Novel compounds and compositions for the inhibition of nampt

ABSTRACT

The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An embodiment of the invention is the provision of a compound of Formula IIIA.

PRIORITY CLAIM

This application claims priority from U.S. provisional application Ser.Nos. 61/379,812, and 61/379,819 both filed Sep. 3, 2010, Ser. No.61/386,037, and 61/386,044 both filed Sep. 24, 2010, Ser. No. 61/478,995filed Apr. 26, 2011 and Ser. No. 61/480,423 filed Apr. 29, 2011, thecontents of which are fully incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to compounds and composition forinhibition of Nicotinamide phosphoribosyltransferase (“NAMPT”), theirsynthesis, applications and antidote.

BACKGROUND OF THE INVENTION

Nicotinamide adenine dinucleotide (NAD) plays fundamental roles in bothcellular energy metabolism and cellular signaling. In energy metabolism,the chemistry of the pyridine ring allows NAD to readily accept anddonate electrons in hydride transfer reactions catalyzed by numerousdehydrogenases.

The preparation of a class of compounds, comprising several subclasses,which act as inhibitors of the formation of nicotinamide adenylnucleotide, and their use thereof as anti-tumor agents, is alreadydescribed in the patent applications WO00/50399, WO97/48695, WO97/48696,WO97/48397, WO99/31063, WO99/31060, WO99/31087, WO99/31064, WO00/50399and WO03/80054.

One of these inhibitors,(E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-(pyridine-3-yl)-acrylamidealso known as APO866, FK866, WK175, or WK22.175 and hereinafter referredto as FK866 [International Non-proprietary Name], is especiallydescribed in the literature as an anticancer agent. FK866 may be usedfor treatment of diseases implicating deregulated apoptosis such ascancer. It has been demonstrated in the prior art that FK866 interfereswith nicotinamide adenyl dinucleotide (also known and hereinafterreferred to as NAD) biosynthesis and induces apoptotic cell deathwithout any DNA damaging effects.

Additionally, FK866 ((E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-(pyridin-3-yl) acrylamide) induces apoptosis in HepG2 cellswithout having primary effects on cellular energy metabolism. (HasmannM, Schemainda I. FK866, a Highly Specific Noncompetitive Inhibitor ofNicotinamide Phosphoribosyltransferase, Represents a Novel Mechanism forInduction of Tumor Cell Apoptosis. Cancer Res 2003; 63:7436-7442.[PubMed: 14612543]) Instead of causing immediate cytotoxicity, itinhibits NAMPT and depletes the cells of NAD, suggesting that FK866could be a promising agent against cancer cells that rely onnicotinamide to synthesize NAD. The crystal structure of the NAMPT-FK866complex reveals that the compound binds at the nicotinamide-binding siteof NAMPT to inhibit its activity. FK866 has been tested in a murinerenal cell carcinoma model and shown to display anti-tumor,antimetastatic, and anti-angiogenic activities (Drevs J, et al.Antiangiogenic potency of FK866/K22.175, a new inhibitor ofintracellular NAD biosynthesis, in murine renal cell carcinoma.Anticancer Res 2003; 23:4853-4858. [PubMed:14981935]).

In a mouse mammary carcinoma model, FK866 also induces a delay in tumorgrowth and an enhancement in tumor radiosensitivity accompanied withdose-dependent decreases in NAD levels, pH, and energy status. Achemosensitizing effect of FK866 has also been observed onanti-neoplastic 1-methyl-3-nitro-1-nitrosoguanidinium (MNNG)-inducedcell death in THP-1 and K562 leukemia cell lines (Pogrebniak A, et al.Chemopotentiating effects of a novel NAD biosynthesis inhibitor, FK866,in combination with antineoplastic agents. Eur J Med Res 2006;11:313-321. [PubMed: 17052966]).

The efficacy of GMX1777 was evaluated in xenograft models and thepharmacokinetic profile of GMX1778 and its effect on nicotinamideadenine dinucleotide cellular levels was measured by liquidchromatography/mass spectrometry. (Beauparlant P., et al. Preclinicaldevelopment of the nicotinamide phosphoribosyl transferase inhibitorprodrug GMX1777. Anticancer Drugs. 2009 June; 20(5):346-54).

GMX1777 is a water-soluble intravenously administered prodrug of GMX1778that Gemin X in-licensed from LEO Pharma (LEO numbers: EB 1627 andCHS828, respectively). These compounds and other substitutedcyanoguanidines have the structures of Table 1. None of the compounds ofthe present invention are cyanoguanidines.

TABLE 1

A

C

B1

B2

Substituted Cyanoguanidines with Defined Pharmacological Effects:

A Cytotoxic CHS 828;

B Potassium channel openers pinacidil (B1) and 12 g of compound asdescribed in Perez-Medrano et al (B2); andc Histamine-II receptor antagonist cimetidine. (from Lövborg et al. BMCResearch Notes 2009₂:114 doi:10.1186/1756-0500-2-114)

More recently, CHS-828 has been identified as a NAMPT inhibitor (OlesenUH, et al. Anticancer agent CHS-828 inhibits cellular synthesis of NAD.Biochem Biophys Res Commun 2008; 367:799-804. [PubMed: 18201551]).CHS-828 has been shown that this compound potently inhibits cell growthin a broad range of tumor cell lines, although the detailed mechanismfor this inhibitory effect of CHS-828 remains undetermined (Ravaud A, etal. Phase I study and guanidine kinetics of CHS-828, aguanidine-containing compound, administered orally as a single doseevery 3 weeks in solid tumors: an ECSG/EORTC study. Eur J Cancer 2005;41:702-707. [PubMed: 15763645]). Both FK866 and CHS-828 are currently inclinical trials for cancer treatments.

There are numerous uses for drugs which inhibit NAMPT.

Lack of NAMPT expression strongly affects development of both T and Blymphocytes. By using mutant forms of this protein and awell-characterized pharmacological inhibitor (FK866), authorsdemonstrated that the ability of the NAMPT to regulate cell viabilityduring genotoxic stress requires its enzymatic activity. Collectively,these data demonstrate that NAMPT participates in cellular resistance togenotoxic/oxidative stress, and it may confer to cells of the immunesystem the ability to survive during stressful situations such asinflammation. (Rongvaux, A., et al. The Journal of Immunology, 2008,181: 4685-4695).

NAMPT may also have effects on endothelium (EC) in relation to highglucose levels, oxidative stress and on aging. It is also believed thatNAMPT may enable proliferating human EC to resist the oxidative stressof aging and of high glucose, and to productively use excess glucose tosupport replicative longevity and angiogenic activity.

SUMMARY OF THE INVENTION

One aspect of this invention is the provision of compounds,compositions, kits, and antidotes for the NAMPT pathway in mammalshaving a compound of the Formula I:

wherein:

-   Ar¹ is aryl, heteroaryl or heterocycloalkyl, wherein the heteroatom    of each of said heteroaryl and heterocycloalkyl numbers 1, 2 or 3,    and is independently selected from N, S or O, further wherein each    of said aryl, heteroaryl and heterocycloalkyl may independently be    either substituted or fused with aryl, heteroaryl or    heterocycloalkyl, still further wherein any of said aryl, heteroaryl    and heterocycloalkyl is either unsubstituted or optionally    independently substituted with one or more substituents which can be    the same or different and are independently selected from the group    consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z),    alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-,    (alkoxyalkyl)amino-, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl,    —N(R³)—C(O)—O— alkyl, —N(R³)—C(O)—O-aryl, -cycloalkyl,    -heterocycloalkyl, -aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl,    with the proviso that no two adjacent ring heteroatoms are both S or    both O;-   X is a straight or branched C₁-C₆ alkyl;-   L is selected from NHC(O)NH, OC(O)NH, NHC(O)O, OCH₂C(O)NH, C(O)NH,    NHC(S)NH, OC(S)NH, NHC(S)O, OCH₂C(S)NH, or C(S)NH;-   A is aryl, heteroaryl, heterocycloalkyl or C₃ to C₈ cycloalkyl, with    each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl being    either unsubstituted or optionally independently substituted with 1,    2, 3 or 4 substituents which can be the same or different and are    independently selected from the group consisting of deuterium, halo,    cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂,    —C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂,    —CH_(z)F_(3-z), —OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, alkoxy-,    -aryloxy-, (alkoxyalkyl)oxy-, (alkoxyalkyl)amino-,    —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —N(R³)—C(O)—O-alkyl,    —N(R³)—C(O)—O-aryl, -cycloalkyl, -heterocycloalkyl,-aryl,    —C(O)-aryl, —S(O)-aryl, and heteroaryl;-   Q is C(O), S(O), S(O)₂;-   R³ is H, alkyl or arylalkyl-;-   z is 0, 1 or 2; and    either:    -   (i) (a) R¹ is selected from H, a straight or branched C₁ to C₇        alkyl, straight or branched C₁ to C₇ alkoxy, straight or        branched C₁ to C₄ hydroxyalkyl, aryl, heteroaryl,        heterocycloalkyl, cycloalkyl, arylalkyl-, heteroarylalkyl-,        heterocycloalkylalkyl-, cycloalkylalkyl-, hydroxyalkyl-,        alkoxyalkyl-, heterospirocycloalkyl and        heterospiroheterocycloalkyl, wherein the heteroatoms of said        heteroaryl and heterocycloalkyl in the moieties above are        independently selected from one or more N, O and S, with the        proviso that no two adjacent ring heteroatoms are both S or both        O, further wherein R¹ can be either unsubstituted or optionally        independently (i) either substituted with one or more        substituents which can be the same or different and are        independently selected from the group consisting of deuterium,        halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-,        —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl),        —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z), alkyl, alkenyl,        alkynyl, hydroxyalkyl-, (hydroxyalkyl)oxy, -alkoxy, carboxy,        (alkoxyalkyl)-, (heteroaryloxy)alkyl-, —NO₂,        (alkoxyalkyl)amino-, -alkylamino, dialkylamino,        (heterocycloalkyloxo)alkyl-, aryloxy, heterocycloalkyloxy-,        aminocarbonyl-, —CHO, —C(O)alkyl, —N(R³)—C(O)-alkyl,        —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃, -cycloalkyl,        alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl,-aryl,        and heteroaryl, or (ii) fused with a cycloalkyl,        -heterocycloalkyl,-aryl, or heteroaryl; and (b) R² is selected        from H, a straight or branched C₁ to C₇ alkyl, straight or        branched C₁ to C₇ alkoxy, straight or branched C₁ to C₄        hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl,        arylalkyl-, heteroarylalkyl-, heterocycloalkylalkyl-,        cycloalkylalkyl-, hydroxyalkyl-, alkoxyalkyl-,        heterospirocycloalkyl and heterospiroheterocycloalkyl, wherein        the heteroatoms of said heteroaryl and heterocycloalkyl in the        moieties above are independently selected from one or more N, O        and S, with the proviso that no two adjacent ring heteroatoms        are both S or both O, further wherein R² can be either        unsubstituted or optionally independently (i) either substituted        with one or more substituents which can be the same or different        and are independently selected from the group consisting of        deuterium, halo, cyano, isocyano, amino, aminoalkyl-,        (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,        —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z),        alkyl, alkenyl, alkynyl, hydroxyalkyl-,        (hydroxyalkyl)oxy,-alkoxy, carboxy, (alkoxyalkyl)-,        (heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,        dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,        heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,        —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,        -cycloalkyl, alkylenedioxy (e.g, methylenedioxy),        -heterocycloalkyl, -aryl, and heteroaryl, or (ii) fused with a        cycloalkyl, -heterocycloalkyl, -aryl, or heteroaryl;-   or (ii) R¹ and R² are joined together to form, along with the N they    are shown attached to in the formula, a C₃-C₈ heterocycloalkyl, a    C₃-C₈ heterocycloalkenyl, a fused bicyclic heterocycloalkyl, a fused    tricyclic heterocycloalkyl, spiroheterocycloalkyl or a    heterospiroheterocycloalkyl, wherein each of said heterocycloalkyl,    heterocycloalkenyl, spiroheterocycloalkyl and    heterospiroheterocycloalkyl can optionally contain one or more    heteroatoms in addition to the N atom they are shown attached to in    the formula, said heteroatoms being selected from N, S and O, with    the proviso that no two adjacent ring heteroatoms are both S or both    O, further wherein each of said heterocycloalkyl, fused bicyclic    heterocycloalkyl, fused tricyclic heterocycloalkyl,    heterocycloalkenyl, spiroheterocycloalkyl and    heterospiroheterocycloalkyl can be either unsubstituted or    optionally independently substituted with one or more substituents    which can be the same or different and are independently selected    from the group consisting of deuterium, halo, cyano, isocyano,    amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),    —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z),    —OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, hydroxyalkyl-,    (hydroxyalkyl)oxy,-alkoxy, carboxy, (alkoxyalkyl)-,    (heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,    dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,    heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,    —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,    -cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl,    -aryl, and heteroaryl;    and pharmaceutically acceptable salts, solvates, esters and isomers    thereof, with the proviso that the compound of Formula I is not    1-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea,    3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea    or    3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

Another aspect of this invention is the provision of compounds ofFormula I where X, L, Q, Ar¹ and A are as defined in Formula I and R¹ isselected from H, a straight or branched C₁ to C₇ alkyl, straight orbranched C₁ to C₇ alkoxy, straight or branched C₁ to C₄ hydroxyalkyl,aryl, heteroaryl, heterocycloalkyl, cycloalkyl, arylalkyl-,heteroarylalkyl-, heterocycloalkylalkyl-, cycloalkylalkyl-,hydroxyalkyl-, alkoxyalkyl-, spiroheterocycloalkyl andheterospiroheterocycloalkyl, wherein the heteroatoms of said heteroaryland heterocycloalkyl in the moieties above are independently selectedfrom one or more N, O and S, with the proviso that no two adjacent ringheteroatoms are both S or both O, further wherein R¹ can be eitherunsubstituted or optionally independently (i) either substituted withone or more substituents which can be the same or different and areindependently selected from the group consisting of deuterium, halo,cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂,—C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂,—CH_(z)F_(3-z), —OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, hydroxyalkyl-,(hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-,(heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,—N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,-cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl,-aryl, and heteroaryl, or (ii) fused with a cycloalkyl,-heterocycloalkyl, -aryl, or heteroaryl; and

R² is selected from H, a straight or branched C₁ to C₇ alkyl, straightor branched C₁ to C₇ alkoxy, straight or branched C₁ to C₄ hydroxyalkyl,aryl, heteroaryl, heterocycloalkyl, cycloalkyl, arylalkyl-,heteroarylalkyl-, heterocycloalkylalkyl-, cycloalkylalkyl-,hydroxyalkyl-, alkoxyalkyl-, spiroheterocycloalkyl andheterospiroheterocycloalkyl, wherein the heteroatoms of said heteroaryland heterocycloalkyl in the moieties above are independently selectedfrom one or more N, O and S, with the proviso that no two adjacent ringheteroatoms are both S or both O, further wherein R² can be eitherunsubstituted or optionally independently (i) either substituted withone or more substituents which can be the same or different and areindependently selected from the group consisting of deuterium, halo,cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂,—C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂,—CH_(z)F_(3-z), —OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, hydroxyalkyl-,(hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-,(heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,—N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,-cycloalkyl, alkylenedioxy (e.g, methylenedioxy),-heterocycloalkyl,-aryl, and heteroaryl, or (ii) fused with acycloalkyl, -heterocycloalkyl,-aryl, or heteroaryl;

and pharmaceutically acceptable salts, solvates, esters and isomersthereof, with the proviso that the compound of Formula I is not1-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea,3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea or3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

Another aspect of this invention is the provision of compounds ofFormula I where X, L, Q, Ar^(t) and A are as defined in Formula I:

-   where R¹ and R² are joined together to form, along with the N they    are shown attached to in the formula, a C₃-C₈ heterocycloalkyl, a    C₃-C₅ heterocycloalkenyl, a fused bicyclic heterocycloalkyl, a fused    tricyclic heterocycloalkyl, spiroheterocyclaolkyl or a    heterospiroheterocycloalkyl, wherein each of said heterocycloalkyl,    heterocycloalkenyl, spiroheterocyclaolkyl and    heterospiroheterocycloalkyl can optionally contain one or more    heteroatoms in addition to the N atom they are shown attached to in    the formula, said heteroatoms being selected from N, S and O, with    the proviso that no two adjacent ring heteroatoms are both S or both    O, further wherein each of said heterocycloalkyl, fused bicyclic    heterocycloalkyl, fused tricyclic heterocycloalkyl,    heterocycloalkenyl, spiroheterocyclaolkyl and    heterospiroheterocycloalkyl can be either unsubstituted or    optionally independently substituted with one or more substituents    which can be the same or different and are independently selected    from the group consisting of deuterium, halo, cyano, isocyano,    amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),    —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z),    —OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, hydroxyalkyl-,    (hydroxyalkyl)oxy,-alkoxy, carboxy, (alkoxyalkyl)-,    (heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,    dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,    heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,    —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,    -cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl,    -aryl, and heteroaryl;    with the proviso that the compound is not    1-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea,    3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea    or    3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

Another aspect of this invention is the provision of compounds,compositions, kits, and antidotes for the NAMPT pathway in mammalshaving a compound of the Formula II:

Ar¹—(CHR)_(n)-L-Ar²—X—R¹  II

wherein

-   Ar¹ is aryl, heteroaryl or heterocycloalkyl, wherein the heteroatom    of each of said heteroaryl and heterocycloalkyl numbers 1, 2 or 3,    and is independently selected from N, S or O, further wherein each    of said aryl, heteroaryl and heterocycloalkyl may independently be    either substituted or fused with aryl, heteroaryl or    heterocycloalkyl, still further wherein any of said aryl, heteroaryl    and heterocycloalkyl is either unsubstituted or optionally    independently substituted with one or more substituents which can be    the same or different and are independently selected from the group    consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z),    alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-,    (alkoxyalkyl)amino-, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl,    —N(R³)—C(O)—O-alkyl, —N(R³)—C(O)—O-aryl, -cycloalkyl,    -heterocycloalkyl, -aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl,    with the proviso that no two adjacent ring heteroatoms are both S or    both O;    R is H, a straight or branched C₁-C₆ alkyl, or arylalkyl;    n is 0, 1, 2, 3 or 4;-   L is selected from NHC(O)NH, OC(O)NH, NHC(O)O, OCH₂C(O)NH, C(O)NH,    NHC(S)NH, OC(S)NH, NHC(S)O, OCH₂C(S)NH, or C(S)NH, with the proviso    that when L is C(O)NH, then n is 0;-   Ar² is aryl, heteroaryl, heterocycloalkyl or C₃ to C₈ cycloalkyl,    with each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl    being either unsubstituted or optionally independently substituted    with 1, 2, 3 or 4 substituents which can be the same or different    and are independently selected from the group consisting of    deuterium, halo, cyano, isocyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z),    alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-,    (alkoxyalkyl)amino-, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl,    —N(R³)—C(O)—O-alkyl, —N(R³)—C(O)—O-aryl, -cycloalkyl,    -heterocycloalkyl,-aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl;

X is S, S(O), S(O)₂, O or C(O);

-   R¹ is cycloalkyl, —CH_(z)F_(3-z), aryl, heterocycloalkyl,    heteroaryl, alkyl, -alkenyl, -alkynyl, (aryl)alkyl-,    (heteroaryl)alkyl- or (heterocycloalkyl)alkyl-, (i) wherein each of    said cycloalkyl, aryl, heterocycloalkyl, heteroaryl and alkyl is    either unsubstituted or optionally substituted with 1, 2, 3, 4 or 5    substituents which can be the same or different and are    independently selected from the group consisting of deuterium, halo,    cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),    —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z),    —OCH_(z)F_(3-z), alkyl, -alkenyl, -alkynyl, alkoxy-, hydroxy,    -alkylhydroxy, aryloxy- or (alkoxyalkyl)amino-, -cycloalkyl,    -heterocycloalkyl,-aryl, —S(O)₂-alkyl, —S(O)₂-aryl, —S(O)₂—CF₃,    —C(O)N(alkyl)₂, —C(O)alkyl, —NH—C(O)-alkyl, —NH—C(O)-aryl,    methylenedioxy, and heteroaryl, (ii) further wherein each of said    cycloalkyl, aryl, heterocycloalkyl, and heteroaryl may additionally    optionally be fused with independently selected aryl, heteroaryl,    heterocycloalkyl or cyloalkyl;    R³ is H, alkyl or arylalkyl-;    z is 0, 1, or 2;    and pharmaceutically acceptable salts, solvates, esters, prodrugs    and isomers thereof, with the proviso that the compound of Formula I    is not    3-{1-[(4-methoxybenzene)sulfonyl]piperidin-4-yl}-1-(pyridin-3-ylmethyl)urea,    or 1-(4-phenoxyphenyl)-3-(pyridin-3-ylmethyl)thiourea.

Another aspect of this invention is the provision of compounds,compositions, kits, and antidotes for the NAMPT pathway in mammalsderived from compounds of Formula I and Formula II and having theformula of Formula III:

wherein:

Ar¹ is 5 to 12 membered heteroaryl comprising 1, 2, 3 or 4 heteroatom(s)independently selected from N, S or O, wherein said heteroaryl isunsubstituted or substituted by one or more R^(a) selected from thegroup consisting of —NH₂, oxo, halo, haloalkyl, —NH(CO)O-alkyl, —C(O)NH₂and 3,4-dihydroxy-5-methyltetrahydrofurane; and wherein said heteroarylcan comprise one or more N-oxide(s) formed with a N atom member of saidheteroaryl, with the proviso that no two adjacent ring heteroatoms areboth S or both O;

Ar² is aryl or 5 or 6 membered heteroaryl comprising 1, 2, 3 or 4heteroatom(s) independently selected from N, S or O;

R is H, a straight or branched C₁-C₆ alkyl, or arylalkyl;

R¹ is —NR³R⁴ wherein R³ is H, alkyl or —S(O)₂alkyl and R⁴ is alkyl,hydroxyalkyl, —S(O)₂alkyl, —(CH₂)_(q)cycloalkyl,—(CH₂)_(q)heterocycloalkyl, aryl, arylalkyl-, —(CH₂)_(q)heteroaryl;

haloalkyl,

cycloalkyl;

aryl;

heterocycloalkyl; or

heteroaryl; wherein:

-   -   (i) each of said cycloalkyl, aryl, heterocycloalkyl or        heteroaryl is unsubstituted or substituted with 1, 2, 3, 4 or 5        substituents which can be the same or different and are        independently selected from the group consisting of:        -   deuterium, halo, cyano, alkyl, hydroxyl, hydroxyalkyl,            hydroxyalkoxy, cyanoalkyl, haloalkyl, alkenyl, alkynyl,            alkoxy, alkylalkoxy, haloalkoxy, arylalkenyl-, aryloxy,            benzyloxy, oxo, —(CH₂)_(q)—NR^(b)R^(c),            —(CH₂)_(q)—CONR^(b)R^(c), —S(O)₂-alkyl, —S(O)₂-aryl,            —S(O)₂NH-alkyl, —S(O)₂N(alkyl)₂, —S(O)₂-heterocycloalkyl,            —S(O)₂—CF₃, —C(O)alkyl, —C(O)aryl, —C(O)alkylenylaryl,            —C(O)O-alkyl, —NH—C(O)alkyl, —NH—C(O)aryl, methylenedioxy,            —(CH₂)_(q)cycloalkyl, cycloalkylalkoxy-, aryl, arylalkyl-,            —(CH₂)_(q)heteroaryl, and —(CH₂)_(q)heterocycloalkyl,            wherein each of said cycloalkyl, heterocycloalkyl, aryl or            heteroaryl may be substituted by one or more halo, nitro,            haloalkyl, haloalkoxy, oxo, cyano, alkyl, haloalkyl, or            alkoxy and;    -   (ii) each of said cycloalkyl, heterocycloalkyl, aryl, or        heteroaryl may optionally additionally be fused with        independently selected aryl, heteroaryl, heterocycloalkyl or        cycloalkyl to from a bicyclic or tricyclic group that may be        substituted by one or more halo, cyano, alkyl or alkoxy;

R² is O or absent,

R^(b) and R^(c) are independently selected from the group consisting ofH, alkyl, hydroxyalkyl, alkoxy, aryl, alkoxyalkyl, —S(O)₂alkyl andcycloalkyl or R^(b) and R^(c) can form a 5 or 6 memberedheterocycloalkyl group together with the nitrogen atom to which they areattached, wherein said heterocycloalkyl group may contain one or moreadditional heteroatom(s) selected from N, S or O;

n is 0, or 1;

q is 0, 1 or 2;

and pharmaceutically acceptable salts, solvates, esters and isomersthereof, with the proviso that the compound of Formula III is not1-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea,3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea or3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

Another embodiment of the invention is the provision of a compound ofFormula III where Ar¹ is pyridine, n is 1, Ar² is phenyl and the Formulabecomes Formula IIIA:

wherein R¹ and R^(a) are as defined in Formula III with the proviso thatthe compounds are notN-[4-(phenylsulfonyl)phenyl]-N′-(3-pyridinylmethyl)urea,N,N-diethyl-4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide,or 4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide.

Another aspect of the invention is compounds of Formula IIIA wherein:

-   R^(a) is more and can be selected from the group consisting of    amino, oxo, halo, halo(C₁-C₆)alkyl, —NH(CO)O—(C₁-C₆)alkyl and    —C(O)NH₂; and wherein said pyridine can comprise a N-oxide formed    with its N atom member;-   R¹ is —NR³R⁴ wherein R³ is H, C₁-C₆-alkyl or —S(O)₂(C₁-C₆)alkyl and    R⁴ is (C₁-C₆)alkyl, hydroxy(C₁-C₆)alkyl, —S(O)₂(C₁-C₆)alkyl,    —(CH₂)_(q)cycloalkyl, —(CH₂)_(q)heterocycloalkyl, aryl,    aryl(C₁-C₆)alkyl-, —(CH₂)_(q)heteroaryl;

halo(C₁-C₆)alkyl,

cycloalkyl;

aryl;

heterocycloalkyl; or

heteroaryl

wherein:

-   -   each of said cycloalkyl, aryl, or heteroaryl is unsubstituted or        substituted with 1, 2, 3, 4 or 5 substituents which can be the        same or different and are independently selected from the group        consisting of:        -   halo, cyano, (C₁-C₆)alkyl, hydroxyl, hydroxy(C₁-C₆)alkyl,            hydroxy(C₁-C₆)alkoxy, halo(C₁-C₆)alkyl, (C₁-C₆)alkoxy,            (C₁-C₆)alkyl(C₁-C₆)alkoxy, halo(C₁-C₆)alkoxy,            aryl(C₂-C₆)alkenyl-, aryloxy, benzyloxy, oxo,            —(CH₂)_(q)—NR^(b)R^(c), —(CH₂)_(q)-CONR^(b)R^(c),            —S(O)₂—(C₁-C₆)alkyl, —S(O)₂NH—(C₁-C₆)alkyl,            —S(O)₂-heterocycloalkyl, —S(O)₂—CF₃, —C(O)(C₁-C₆)alkyl,            —C(O)aryl, —C(O) (C₂-C₆)alkylenylaryl, —C(O)O—(C₁-C₆)alkyl,            —(CH₂)_(q)cycloalkyl, cycloalkyl(C₁-C₆)alkoxy-, aryl,            aryl(C₁-C₆)alkyl-, —(CH₂)_(q)heteroaryl, and            —(CH₂)_(q)heterocycloalkyl, wherein each of said cycloalkyl,            heterocycloalkyl, aryl or heteroaryl may be substituted by            one or more halo, nitro, halo(C₁-C₆)alkyl,            halo(C₁-C₆)alkoxy, oxo, cyano, (C₁-C₆)alkyl,            halo(C₁-C₆)alkyl, or (C₁-C₆)alkoxy;

-   R^(b) and R^(c) are independently selected from the group consisting    of H, (C₁-C₆)alkyl, hydroxy(C₁-C₆)alkyl, (C₁-C₆)alkoxy, aryl,    (C₁-C₆)alkoxy(C₁-C₆)alkyl, —S(O)₂(C₁-C₆)alkyl and (C₃-C₆)cycloalkyl    or R^(b) and R^(c) can form a 5 or 6 membered heterocycloalkyl group    together with the nitrogen atom to which they are attached, wherein    said heterocycloalkyl group may contain one or more additional    heteroatom(s) selected from N, S or O    q is 0 or 1; and    pharmaceutically acceptable salts thereof,    with the proviso that the compound of Formula IIIA is not:    N-[4-(phenylsulfonyl)phenyl]-N′-(3-pyridinylmethyl)urea,    N,N-diethyl-4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide,    or 4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide.

Another aspect of this invention is the provision of methods of treatinga disease via the inhibition of NAMPT in a subject (e.g., a human) inneed thereof by administering to the subject an effective amount of thecompound or the pharmaceutical formulation of the present invention.

Still another aspect of this invention is to provide a method fortreating, preventing, inhibiting or eliminating a disease or conditionin a patient by inhibiting NAMPT in said patient by administering atherapeutically affective amount of at least one compound of thisdisclosure, wherein said disease or condition is selected from the groupconsisting of cancer, ovarian cancer, breast cancer, uterine cancer,colon cancer, cervical cancer, lung cancer, prostate cancer, skincancer, bladder cancer, pancreatic cancer, leukemia, lymphoma, Hodgkin'sdisease, viral infections, Human Immunodeficiency Virus, hepatitisvirus, herpes virus, herpes simplex, inflammatory disorders, irritablebowel syndrome, inflammatory bowel disease, rheumatoid arthritis,asthma, chronic obstructive pulmonary disease, osteoarthritis,osteaoporosis, dermatitis, atoptic dermatitis, psoriasis, systemic lupuserythematosis, multiple sclerosis, psoriatic arthritis, ankylosingspondylitis, gragt-versus-host disease, Alzhemier's disease,cerbrovascular accident, artherosclerosis, diabetes,glomerulonephritits, metabolic syndrome, non-small cell lung cancer,small cell lung cancer, multiple myeloma, leukemia, lymphomas, squamouscell cancers, kidney cancer, uretral and bladder cancers, cancers ofhead and neck, cancers of the brain and central nervous system.

Another preferred embodiment is a pharmaceutical formulation comprisinga pharmaceutically acceptable compound of the present invention, whichprovides, upon administration to a human, a decrease in tumor burdenand/or metastases. The pharmaceutical formulation can be administered byoral means or other suitable means.

Yet another embodiment is a method of treating ovarian cancer in asubject (e.g., a human) in need thereof by administering to the subjectan effective amount of the compound or the pharmaceutical formulation ofthe present invention.

Yet another embodiment is a method of treating colon cancer in a subject(e.g., a human) in need thereof by administering to the subject aneffective amount of the compound or the pharmaceutical formulation ofthe present invention.

Yet another embodiment is a method of treating breast cancer in asubject (e.g., a human) in need thereof by administering to the subjectan effective amount of the pharmaceutical formulation of the presentinvention. in a subject (e.g., a human) in need thereof by administeringto the subject an effective amount of the compound or the pharmaceuticalformulation of the present invention.

Yet another embodiment is a method of treating leukemia in a subject(e.g., a human) in need thereof by administering to the subject aneffective amount of the compound or the pharmaceutical formulation ofthe present invention.

Yet another embodiment is a method of treating colon cancer, before orafter surgical resection and/or radiation therapy, in a subject (e.g., ahuman) in need thereof by administering to the subject an effectiveamount of the compound or the pharmaceutical formulation of the presentinvention.

Yet another embodiment is a method of treating cancer, before or aftersurgical resection and/or radiation therapy, in a subject (e.g., ahuman) in need thereof by administering to the subject an effectiveamount of the compound or the pharmaceutical formulation of the presentinvention, including adjunctive therapy to treat nausea, with or withoutdexamethasone.

Yet another embodiment is a method of treating cancer, before or aftersurgical resection and or radiation therapy, in a subject (e.g., ahuman) in need thereof by administering to the subject an effectiveamount of the compound or the pharmaceutical formulation of the presentinvention, including adjunctive therapy with one or more additionaltherapeutic agents, or their pharmaceutically acceptable salts thereof.Non-limiting examples of such additional therapeutic agents includecytotoxic agents (such as for example, but not limited to, DNAinteractive agents (such as cisplatin or doxorubicin)); taxanes (e.g.taxotere, taxol); topoisomerase II inhibitors (such as etoposide);topoisomerase I inhibitors (such as irinotecan (or CPT-11), camptostar,or topotecan); tubulin interacting agents (such as paclitaxel, docetaxelor the epothilones); hormonal agents (such as tamoxifen); thymidilatesynthase inhibitors (such as 5-fluorouracil or 5-FU); anti-metabolites(such as methoxtrexate); alkylating agents (such as temozolomide,cyclophosphamide); Farnesyl protein transferase inhibitors (such as,SARASAR™.(4-[2-[4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,-6]cyclohepta[1,2-b]pyridin-11-yl-]-1-piperidinyl]-2-oxoehtyl]-1-piperidine-carboxamide,or SCH 66336), tipifarnib (Zarnestra® or R115777 from JanssenPharmaceuticals), L778,123 (a farnesyl protein transferase inhibitorfrom Merck & Company, Whitehouse Station, N.J.), BMS 214662 (a farnesylprotein transferase inhibitor from Bristol-Myers Squibb Pharmaceuticals,Princeton, N.J.); signal transduction inhibitors (such as, Iressa® (fromAstra Zeneca Pharmaceuticals, England), Tarceva® (EGFR kinaseinhibitors), antibodies to EGFR (e.g., C225), GLEEVEC® (C-abl kinaseinhibitor from Novartis Pharmaceuticals, East Hanover, N.J.);interferons such as, for example, Intron® (from Merck & Company),Peg-Intron® (from Merck & Company); hormonal therapy combinations;aromatase combinations; ara-C, adriamycin, cytoxan, and gemcitabine.

Other anti-cancer (also known as anti-neoplastic) agents include but arenot limited to Uracil mustard, Chlormethine, Ifosfamide, Melphalan,Chlorambucil, Pipobroman, Triethylenemelamine,Triethylenethiophosphoramine, Busulfan, Carmustine, Lomustine,Streptozocin, Dacarbazine, Floxuridine, Cytarabine, 6-Mercaptopurine,6-Thioguanine, Fludarabine phosphate, oxaliplatin, leucovirin,oxaliplatin (ELOXATIN®. from Sanofi-Synthelabo Pharmaceuticals, France),Pentostatine, Vinblastine, Vincristine, Vindesine, Bleomycin,Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin,Mithramycin, Deoxycoformycin, Mitomycin-C, L-Asparaginase, Teniposide17α-Ethinylestradiol, Diethylstilbestrol, Testosterone, Prednisone,Fluoxymesterone, Dromostanolone propionate, Testolactone,Megestrolacetate, Methylprednisolone, Methyltestosterone, Prednisolone,Triamcinolone, Chlorotrianisene, Hydroxyprogesterone, Aminoglutethimide,Estramustine, Medroxyprogesteroneacetate, Leuprolide, Flutamide,Toremifene, goserelin, Cisplatin, Carboplatin, Hydroxyurea, Amsacrine,Procarbazine, Mitotane, Mitoxantrone, Levamisole, Navelbene,Anastrazole, Letrazole, Capecitabine, Reloxafine, Droloxafine,Hexamethylmelamine, Avastin, herceptin, Bexxar, Velcade®, Zevalin,Trisenox, Xeloda, Vinorelbine, Porfimer, Erbitux, Liposomal, Thiotepa,Altretamine, Melphalan, Trastuzumab, Lerozole, Fulvestrant, Exemestane,Ifosfomide, Rituximab, C225, and Campath, 5-fluorouracil and leucovorin,with or without a 5-HT₃ receptor inhibitor (e.g., dolansetron,granisetron, ondansetron) with or without dexamethasone.

If formulated as a fixed dose, such combination products employ thecompounds of this invention within the dosage range described herein (oras known to those skilled in the art) and the other pharmaceuticallyactive agents or treatments within its dosage range. For example, theCDC2 inhibitor olomucine has been found to act synergistically withknown cytotoxic agents in inducing apoptosis (J. Cell Sci., (1995) 108,2897). The compounds of the invention may also be administeredsequentially with known anticancer or cytotoxic agents when acombination formulation is inappropriate. In any combination treatment,the invention is not limited in the sequence of administration;compounds of Formula (I) may be administered either prior to or afteradministration of the known anticancer or cytotoxic agent. For example,the cytotoxic activity of the cyclin-dependent kinase inhibitorflavopiridol is affected by the sequence of administration withanticancer agents. Cancer Research, (1997) 57, 3375. Such techniques arewithin the skills of persons skilled in the art as well as attendingphysicians.

Any of the aforementioned methods may be augmented by administration offluids (such as water), loop diuretics, one or more of achemotherapeutic or antineoplastic agent, such as leucovorin andfluorouracil, and an adjunctive chemotherapeutic agent (such asfilgrastim and erythropoietin), or any combination of the foregoing.

Yet another embodiment is a method for administering a compound of theinstant invention to a subject (e.g., a human) in need thereof byadministering to the subject the pharmaceutical formulation of thepresent invention.

Yet another embodiment is a method of preparing a pharmaceuticalformulation of the present invention by mixing at least onepharmaceutically acceptable compound of the present invention, and,optionally, one or more pharmaceutically acceptable additives orexcipients.

For preparing pharmaceutical compositions from the compounds describedby this invention, inert, pharmaceutically acceptable carriers can beeither solid or liquid. Solid form preparations include powders,tablets, dispersible granules, capsules, cachets and suppositories. Thepowders and tablets may be comprised of from about 5 to about 95 percentactive ingredient. Suitable solid carriers are known in the art, e.g.,magnesium carbonate, magnesium stearate, talc, sugar or lactose.Tablets, powders, cachets and capsules can be used as solid dosage formssuitable for oral administration. Examples of pharmaceuticallyacceptable carriers and methods of manufacture for various compositionsmay be found in A. Gennaro (ed.), Remington's Pharmaceutical Sciences,18th Edition, (1990), Mack Publishing Co., Easton, Pa.

Liquid form preparations include solutions, suspensions and emulsions.As an example may be mentioned water or water-propylene glycol solutionsfor parenteral injection or addition of sweeteners and opacifiers fororal solutions, suspensions and emulsions. Liquid form preparations mayalso include solutions for intranasal administration.

Aerosol preparations suitable for inhalation may include solutions andsolids in powder form, which may be in combination with apharmaceutically acceptable carrier, such as an inert compressed gas,e.g. nitrogen.

Also included are solid form preparations that are intended to beconverted, shortly before use, to liquid form preparations for eitheroral or parenteral administration. Such liquid forms include solutions,suspensions and emulsions.

The compounds of the invention may also be deliverable transdermally.The transdermal compositions can take the form of creams, lotions,aerosols and/or emulsions and can be included in a transdermal patch ofthe matrix or reservoir type as are conventional in the art for thispurpose.

The compounds of this invention may also be delivered subcutaneously.

Preferably the compound is administered orally or intravenously.

Preferably, the pharmaceutical preparation is in a unit dosage form. Insuch form, the preparation is subdivided into suitably sized unit dosescontaining appropriate quantities of the active component, e.g., aneffective amount to achieve the desired purpose.

The quantity of active compound in a unit dose of preparation may bevaried or adjusted from about 1 mg to about 1000 mg, preferably fromabout 1 mg to about 500 mg, more preferably from about 1 mg to about 250mg, still more preferably from about 1 mg to about 25 mg, according tothe particular application.

The actual dosage employed may be varied depending upon the requirementsof the patient and the severity of the condition being treated.Determination of the proper dosage regimen for a particular situation iswithin the skill of the art. For convenience, the total daily dosage maybe divided and administered in portions during the day as required.

The amount and frequency of administration of the compounds of theinvention and/or the pharmaceutically acceptable salts thereof will beregulated according to the judgment of the attending clinicianconsidering such factors as age, condition and size of the patient aswell as severity of the symptoms being treated. A typical recommendeddaily dosage regimen for oral administration can range from about 1mg/day to about 500 mg/day, preferably 1 mg/day to 200 mg/day, in two tofour divided doses.

Another aspect of the invention is a pharmaceutical compositioncomprising a compound according to the invention and a cell rescuingagent. In a certain embodiment according to the invention, the cellrescuing agent is selected from the group consisting of nicotinamide,nicotinamide mononucleotide (NMN) and nicotinic acid.

Definitions

As used above, and throughout this disclosure, the following terms,unless otherwise indicated, shall be understood to have the followingmeanings. If a definition is missing, convention definition as known toone skilled in the art controls.

“Patient” includes both human and animals.

“Mammal” means humans and other mammalian animals.

The term “inhibitor” refers to a molecule such as a compound, a drug, anenzyme activator or a hormone that blocks or otherwise interferes with aparticular biologic activity.

The terms “effective amount” or “therapeutically effective amount” referto a sufficient amount of the agent to provide the desired biologicalresult. That result can be reduction and/or alleviation of the signs,symptoms, or causes of a disease, or any other desired alteration of abiological system. For example, an “effective amount” for therapeuticuse is the amount of the composition comprising a compound as disclosedherein required to provide a clinically significant decrease in adisease. An appropriate “effective” amount in any individual case may bedetermined by one of ordinary skill in the art using routineexperimentation. Thus, the expression “effective amount” generallyrefers to the quantity for which the active substance has therapeuticeffects. In the present case the active substance is the inhibitor ofthe formation of Nicotinamide phosphoribosyltransferase (NAMPT).

As used herein, the terms “treat” or “treatment” are synonymous with theterm “prevent” and are meant to indicate a postponement of developmentof diseases, preventing the development of diseases, and/or reducingseverity of such symptoms that will or are expected to develop. Thus,these terms include ameliorating existing disease symptoms, preventingadditional symptoms, ameliorating or preventing the underlying metaboliccauses of symptoms, inhibiting the disorder or disease, e.g., arrestingthe development of the disorder or disease, relieving the disorder ordisease, causing regression of the disorder or disease, relieving acondition caused by the disease or disorder, or stopping the symptoms ofthe disease or disorder.

By “pharmaceutically acceptable” or “pharmacologically acceptable” ismeant a material which is not biologically or otherwise substantiallyundesirable, i.e., the material may be administered to an individualwithout causing any substantially undesirable biological effects orinteracting in a deleterious manner with any of the components of thecomposition in which it is contained.

“Carrier materials” or what are also referred to as “excipients” includeany commonly used excipients in pharmaceutics and should be selected onthe basis of compatibility and the release profile properties of thedesired dosage form. Exemplary carrier materials include, e.g., binders,suspending agents, disintegration agents, filling agents, surfactants,solubilizers, stabilizers, lubricants, wetting agents, diluents, and thelike. “Pharmaceutically compatible carrier materials” may comprise,e.g., acacia, gelatin, colloidal silicon dioxide, calciumglycerophosphate, calcium lactate, maltodextrin, glycerine, magnesiumsilicate, sodium caseinate, soy lecithin, sodium chloride, tricalciumphosphate, dipotassium phosphate, sodium stearoyl lactylate,carrageenan, monoglyceride, diglyceride, pregelatinized starch, and thelike. See, e.g., Hoover, John E., Remington's Pharmaceutical Sciences,Mack Publishing Co., Easton, Pa. 1975.

As used herein, the term “subject” encompasses mammals and non-mammals.Examples of mammals include, but are not limited to, any member of theMammalian class: humans, non-human primates such as chimpanzees, andother apes and monkey species; farm animals such as cattle, horses,sheep, goats, swine; domestic animals such as rabbits, dogs, and cats;laboratory animals including rodents, such as rats, mice and guineapigs, and the like. Examples of non-mammals include, but are not limitedto, birds, fish and the like. In one embodiment of the presentinvention, the mammal is a human.

As used herein, “alkyl” means a straight chain or branched saturatedchain having from 1 to 10 or 1 to 6 (C₁-C₆) carbon atoms. Representativesaturated alkyl groups include, but are not limited to, methyl, ethyl,n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl,2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl,2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl,4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl,4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl,2-ethyl-1-butyl, butyl, isobutyl, t-butyl, n-pentyl, isopentyl,neopentyl, n-hexyl and the like, and longer alkyl groups, such asheptyl, and octyl and the like. An alkyl group can be unsubstituted orsubstituted. Alkyl groups containing three or more carbon atoms may bestraight, branched or cyclized. As used herein, “lower alkyl” means analkyl having from 1 to 6 carbon atoms.

As used herein, an “alkenyl group” includes an unbranched or branchedhydrocarbon chain having one or more double bonds therein. The doublebond of an alkenyl group can be unconjugated or conjugated to anotherunsaturated group. Illustrative alkenyl groups include, but are notlimited to, (C₂-C₈) or (C₂-C₆) alkenyl groups, such as ethylenyl, vinyl,allyl, butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, hexadienyl,2-ethylhexenyl, 2-propyl-2-butenyl, 4-(2-methyl-3-butene)-pentenyl andthe like. An alkenyl group can be unsubstituted or substituted.

The term “hydroxyalkyl” denotes an alkyl group as defined above whereinat least one of the hydrogen atoms of the alkyl group is replaced by ahydroxy group. Examples of hydroxyalkyl include, but are not limited to,meththyl, ehtyl propyl, isopropyl, isobutryl, sec-butyl, tert-butyl,pentyl or n-hexyl wherein one or more hydrogen atoms are replaced by OH,as well as those hydroxyalkyl groups specifically illustrated b theexamples herein below.

As used herein, “alkynyl group” includes an unbranched or branchedhydrocarbon chain having one or more triple bonds therein. The triplebond of an alkynyl group can be unconjugated or conjugated to anotherunsaturated group. Suitable alkynyl groups include, but are not limitedto, (C₂-C₆) alkynyl groups, such as ethynyl, propynyl, butynyl,pentynyl, hexynyl, methylpropynyl, 4-methyl-1-butynyl,4-propyl-2-pentynyl, 4-butyl-2-hexynyl and the like. An alkynyl groupcan be unsubstituted or substituted.

The term “haloalkyl” denotes an alkyl group as defined above wherein atleast one of the hydrogen atoms of the alkyl group is replaced by ahalogen atom, preferably fluoro or chloro, most preferably fluoro.Examples of haloalkyl include, but are not limited to, methyl, ethyl,propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, pentyl or n-hexylwherein one or more hydrogen atoms are replaced by Cl, F, Br or Iatom(s), as well as those haloalkyl groups specifically illustrated bythe examples herein below. Among the preferred halloalkyl groups aremonofluoro-, difluoro- or trifluoro-methyl, -ethyl or -propyl, forexample 3,3,3,-trifluoropropyl, 2-fluroethyl, 2,2,2-trifluoroethyl,fluoromethyl, trifluoromethyl.

The terms “trifluoromethyl,” “sulfonyl,” and “carboxyl” include CF₃,SO₂, and CO₂H, respectively.

The term “oxo” means a=O group.

The term alkylhydroxy or hydroxyalkyl means an alkyl group as definedabove, wherein at least one of the hydrogen atoms of the alkyl group isreplaced by an OH group.

The term “alkoxy” as used herein includes —O-(alkyl), wherein alkyl isdefined above.

The term “haloalkoxy” denotes an alkoxy group as defined above whereinat least one of the hydrogen atoms of the alkoxy group is replaced by ahalogen atom, preferably fluoro or chloro, most preferably fluoro.

The term “hydroxyalkoxy” means an alkoxy group as defined herein,wherein at least one of the hydrogen atoms of the alkoxy group isreplaced by an OH group.

The term “aminoalkyl” as used herein means a group having one or morenitrogen atoms and one or more alkyl groups as defined above on thenitrogen.

“Aralkyl” or “arylalkyl” means an aryl-alkyl-group in which the aryl andalkyl are as previously described. Preferred aralkyls comprise a loweralkyl group. Non-limiting examples of suitable aralkyl groups includebenzyl, 2-phenethyl and naphthalenylmethyl. The bond to the parentmoiety is through the alkyl.

“Heteroarylalkyl” means a heteroaryl moiety as defined herein linked viaan alkyl moiety (defined above) to a parent core. Non-limiting examplesof suitable heteroaryls include 2-pyridinylmethyl, quinolinylmethyl andthe like.

“Heterocyclylalkyl” means a heterocyclyl moiety as defined herein linkedvia an alkyl moiety (defined above) to a parent core. Non-limitingexamples of suitable heterocyclylalkyls include piperidinylmethyl,piperazinylmethyl and the like.

It should also be noted that any carbon as well as heteroatom withunsatisfied valences in the text, schemes, examples and Tables herein isassumed to have the sufficient number of hydrogen atom(s) to satisfy thevalences.

When any variable (e.g., aryl, heterocycle, R², etc.) occurs more thanone time in any constituent or in the Formulas, its definition on eachoccurrence is independent of its definition at every other occurrence.

The term “N-oxide(s) forms with a N atom member of said heteroaryl”denotes a heteroaryl group containing a nitrogen atom that forms aN-oxide. Illustrative and non limiting examples of such N-oxides are:

The expression: “wherein said pyridine can comprise a N-oxide formedwith its N atom member” denotes the following formula:

As used herein, the term “composition” is intended to encompass aproduct comprising the specified ingredients in the specified amounts,as well as any product which results, directly or indirectly, fromcombination of the specified ingredients in the specified amounts.

The term “deuterium” as used herein means a stable isotope of hydrogenhaving odd numbers of protons and neutrons.

The term “halo” as used herein means a substituent having at least onehalogen selected from fluorine, chlorine, bromine, and iodine.

The term “cyano” as used herein means a substituent having a carbon atomjoined to a nitrogen atom by a triple bond.

The term “amino” as used herein means a substituent containing at leastone nitrogen atom.

The term “(amino)alkoxy” as used herein means a substituent having atleast one amino group and at least one alkoxy group.

The term “aryloxy” as used herein means a substituent of the form Ar-O—where Ar is an aryl group as defined herein.

The term “benzyloxy” denotes a benzyl-O-group.

The term “arylalkenyl” denotes an aryl group, as defined herein,attached to the rest of the molecule by an alkenyl group as definedherein.

The term “cycloalkylalkoxy-” denotes a cycloalkyl group as definedherein, attached to the rest of the molecule by an alkoxy group asdefined herein.

The term “methylenedioxy” as used herein means a functional group withthe structural formula —O—CH₂—O— which is connected to the molecule bytwo chemical bonds via the oxygens.

As used herein, “alkoxyalkyl” means-(alkyl)-O-(alkyl), wherein each“alkyl” is independently an alkyl group defined above.

The term “(alkoxyalkyl)amino” as used herein means a substituent havingat least one alkoxyalkyl group as defined above and at least one aminogroup as defined above.

The term “spirocycloalkyl” as used herein means a spiro group(containing no heteroatom) linked in a spiro manner to a cycloalkylgroup. A non-limiting example would be the moiety shown below:

The term “spiroheterocycloalkyl” as used herein means a spiro group(containing no heteroatom) linked in a spiro manner to aheterocycloalkyl group. A non-limiting example would be the moiety shownbelow:

The term “heterospiroheterocycloalkyl” as used herein means a spirogroup (containing a hetero atom such O, N or S) linked in a spiro mannerto a heterocycloalkyl group. A non-limiting example would be the moietyshown below:

“Aryl” as used herein means a monovalent aromatic hydrocarbon radical of6-20 or 6-10 carbon atoms derived by the removal of one hydrogen atomfrom a single carbon atom of a parent aromatic ring system. Arylincludes bicyclic radicals comprising an aromatic ring fused to asaturated, partially unsaturated ring, or aromatic carbocyclic orheterocyclic ring. Exemplary aryl groups include, but are not limitedto, radicals derived from benzene, naphthalene, anthracene, biphenyl,indene, indane, 1,2-dihydronapthalene, 1,2,3,4-tetrahydronapthalene, andthe like. Aryl groups may be optionally substituted independently withone or more substituents described herein. Illustrative examples of arylgroups include, but are not limited to, the following moieties:

and the like.

Illustrative substituted aryls include:

and the like.

As used herein, the term “heteroaryl” refers to a monocyclic, or fusedpolycyclic, aromatic heterocycle (ring structure having ring atomsselected from carbon atoms as well as nitrogen, oxygen, and sulfurheteroatoms) having from 3 to 24 ring atoms per ring. The term“heteroaryl” as used herein also includes monovalent aromatic radical ofa 5-, 6-, or 7-membered ring and includes fused ring systems (at leastone of which is aromatic) of 5-10 atoms containing at least oneheteroatom independently selected from nitrogen, oxygen, and sulfur.Examples of heteroaryl groups include, but are not limited to,pyridinyl, imidazolyl, imidazopyridinyl, pyrimidinyl, pyrazolyl,triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl,oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl,benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl,phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl,oxadiazolyl, triazolyl, thiadiazolyl, thiadiazolyl, furazanyl,benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl,quinazolinyl, quinoxalinyl, naphthyridinyl, and furopyridinyl. Spiromoieties are also included within the scope of this definition.Heteroaryl groups may be optionally substituted independently with oneor more substituents described herein. 5 or 6 membered heteroaryl can beselected from the group consisting of optionally substituted pyridinyl,pyrimidinyl, thiazolyl, imidazolyl, oxazolyl, isoxazolyl, pyrazolyl,pyridinone and benzimidazolyl.

By way of example and not limitation, carbon bonded heterocycles andheteroaryls are bonded at position 2, 3, 4, 5, or 6 of a pyridine,position 3, 4, 5, or 6 of a pyridazine, position 2, 4, 5, or 6 of apyrimidine, position 2, 3, 5, or 6 of a pyrazine, position 2, 3, 4, or 5of a furan, tetrahydrofuran, thiofuran, thiophene, pyrrole ortetrahydropyrrole, position 2, 4, or 5 of an oxazole, imidazole orthiazole, position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole,position 2 or 3 of an aziridine, position 2, 3, or 4 of an azetidine,position 2, 3, 4, 5, 6, 7, or 8 of a quinoline or position 1, 3, 4, 5,6, 7, or 8 of an isoquinoline. Further examples of carbon bondedheterocycles include 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl,6-pyridyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl,3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, or5-thiazolyl.

By way of example and not limitation, nitrogen bonded heterocycles andheteroaryls are bonded at position 1 of an aziridine, azetidine,pyrrole, pyrrolidine, 2-pyrroline, 3-pyrroline, imidazole,imidazolidine, 2-imidazoline, 3-imidazoline, pyrazole, pyrazoline,2-pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline,1H-indazole, position 2 of an isoindole, or isoindoline, position 4 of amorpholine, and position 9 of a carbazole, or β-carboline. Still moretypically, nitrogen bonded heterocycles include 1-aziridyl, 1-azetedyl,1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, and 1-piperidinyl.

Illustrative examples of heteroaryl and substituted heteroaryl groupsinclude, but are not limited to the following moieties:

and the like.

The term “bicyclic heteroaryl” means a structure having atoms arrangedin two rings fused together with at least two atoms common to each ring,and at least one of the rings being a heteroaryl ring. Non limitingexamples of bicyclic hetroaryl comprise 5 to 13 or 5 to 10 memberedbicyclic heteroaryl-groups comprising 1, 2, 3 or 4 heteroatomsindependently selected from N, S, or O:

and the like.

Further examples of bicyclic heteroaryls include but are not limited to:

These bicyclic heteroaryl groups can be substituted as defined herein.

As used herein, the term “cycloalkyl” refers to a saturated or partiallysaturated, monocyclic or fused or spiro polycyclic, carbocycle havingfrom 3 to 24 (C₃-C₂₄), 3 to 12(C₃-C₁₂), 3 to 10 (C₃-C₁₀) or 3 to 6(C₃-C₆) ring atoms per ring. Illustrative examples of cycloalkyl groupsinclude, but are not limited to, the following moieties:

and the like.

As used herein, the term “heterocycloalkyl” refers to a monocyclic, orfused or spiro, polycyclic, ring structure that is saturated orpartially saturated and has from 3 to 24 ring atoms per ring selectedfrom C atoms and N, O, and S heteroatoms. Illustrative examples ofheterocycloalkyl and substituted heterocycloalkyl groups include, butare not limited to:

and the like.

Numerical ranges, as used herein, are intended to include sequentialwhole numbers. For example, a range expressed as “from 0 to 4” wouldinclude 0, 1, 2, 3 and 4.

As used herein, the term “substituted” means that the specified group ormoiety bears one or more suitable substituents.

As used herein, the term “unsubstituted” means that the specified groupbears no substituents.

As used herein, the term “optionally substituted” means that thespecified group is unsubstituted or substituted by one or moresubstituents.

When a multifunctional moiety is shown, the point of attachment to thecore is indicated by a line. For e.g. (cycloalkyloxy)alkyl- refers toalkyl being the point of attachment to the core while cycloalkyl isattached to alkyl via the oxy group.

The expression “adjunctive chemotherapeutic agent” generally refers toagents which treat, alleviate, relieve, or ameliorate the side effectsof chemotherapeutic agents. Such agents include those which modify bloodcell growth and maturation. Examples of adjunctive chemotherapeuticagents include, but are not limited to, filgrastim and erythropoietin.Other such adjunctive chemotherapeutic agents include those whichinhibit nausea associated with administration of the chemotherapeuticagents, such as a 5-HT₃ receptor inhibitor (e.g., dolansetron,granisetron, or ondansetron), with or without dexamethasone.

The terms “chemotherapeutic agent” and “antineoplastic agent” generallyrefer to agents, which treat, prevent, cure, heal, alleviate, relieve,alter, remedy, ameliorate, improve, or affect malignancies and theirmetastasis. Examples of such agents (also known as “antineoplasticagents”) include, but are not limited to, prednisone, fluorouracil(e.g., 5-fluorouracil (5-FU)), anastrozole, bicalutamide, carboplatin,cisplatin, chlorambucil, cisplatin, carboplatin, docetaxel, doxorubicin,flutamide, interferon-alpha, letrozole, leuprolide, megestrol,mitomycin, oxaliplatin, paclitaxel, plicamycin (Mithracin™), tamoxifen,thiotepa, topotecan, valrubicin, vinvlastin, vincristine, and anycombination of any of the foregoing. Additional such agents aredescribed later.

“Nicotinamide phosphoribosyltransferase” also named NAMPT, NMPRT,NMPRTase or NAmPRTase, (International nomenclature: E.C. 2.4.2.12) is akey enzyme in nicotinamide adenyl dinucleotide (NAD) biosynthesis fromthe natural precursor nicotinamide.

It must be noted that, as used in the specification and the appendedclaims, the singular forms “a,” “an” and “the” include plural referentsunless the context clearly dictates otherwise.

When used as a therapeutic agent the inhibitors of the formation ofnicotinamide phosphoribosyltransferase (NAMPT) described herein may beadministered with one or more physiologically acceptable excipients. Aphysiologically acceptable carrier or excipient is a formulation towhich the compound can be added to dissolve it or otherwise facilitateits administration.

The dosage forms of the present invention, may contain a mixture of oneor more compounds of this invention, and may include additionalmaterials known to those skilled in the art as pharmaceuticalexcipients. Such pharmaceutical excipients include, for example, thefollowing: Stabilizing additives may be incorporated into the deliveryagent solution. With some drugs, the presence of such additives promotesthe stability and dispersibility of the agent in solution. Thestabilizing additives may be employed at a concentration ranging fromabout 0.1 and 5% (W/V), preferably about 0.5% (W/V). Suitable, butnon-limiting, examples of stabilizing additives include gum acacia,gelatin, methyl cellulose, polyethylene glycol, carboxylic acids andsalts thereof, and polylysine. The preferred stabilizing additives aregum acacia, gelatin and methyl cellulose.

Acidifying agents (acetic acid, glacial acetic acid, citric acid,fumaric acid, hydrochloric acid, diluted hydrochloric acid, malic acid,nitric acid, phosphoric acid, diluted phosphoric acid, sulfuric acid,tartaric acid); Aerosol propellants (butane, dichlorodifluoro-methane,dichlorotetrafluoroethane, isobutane, propane,trichloromonofluoromethane); Air displacements (carbon dioxide,nitrogen); Alcohol denaturants (denatonium benzoate, methyl isobutylketone, sucrose octacetate); Alkalizing agents (strong ammonia solution,ammonium carbonate, diethanolamine, diisopropanolamine, potassiumhydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodiumhydroxide, trolamine); Anticaking agents (see glidant); Antifoamingagents (dimethicone, simethicone); Antimicrobial preservatives(benzalkonium chloride, benzalkonium chloride solution, benzelthoniumchloride, benzoic acid, benzyl alcohol, butylparaben, cetylpyridiniumchloride, chlorobutanol, chlorocresol, cresol, dehydroacetic acid,ethylparaben, methylparaben, methylparaben sodium, phenol, phenylethylalcohol, phenylmercuric acetate, phenylmercuric nitrate, potassiumbenzoate, potassium sorbate, propylparaben, propylparaben sodium, sodiumbenzoate, sodium dehydroacetate, sodium propionate, sorbic acid,thimerosal, thymol); Antioxidants (ascorbic acid, acorbyl palmitate,butylated hydroxyanisole, butylated hydroxytoluene, hypophosphorousacid, monothioglycerol, propyl gallate, sodium formaldehyde sulfoxylate,sodium metabisulfite, sodium thiosulfate, sulfur dioxide, tocopherol,tocopherols excipient); Buffering agents (acetic acid, ammoniumcarbonate, ammonium phosphate, boric acid, citric acid, lactic acid,phosphoric acid, potassium citrate, potassium metaphosphate, potassiumphosphate monobasic, sodium acetate, sodium citrate, sodium lactatesolution, dibasic sodium phosphate, monobasic sodium phosphate); Capsulelubricants (see tablet and capsule lubricant); Chelating agents (edetatedisodium, ethylenediaminetetraacetic acid and salts, edetic acid);Coating agents (sodium carboxymethylcellulose, cellulose acetate,cellulose acetate phthalate, ethylcellulose, gelatin, pharmaceuticalglaze, hydroxypropyl cellulose, hydroxypropyl methylcellulose,hydroxypropyl methylcellulose phthalate, methacrylic acid copolymer,methylcellulose, polyethylene glycol, polyvinyl acetate phthalate,shellac, sucrose, titanium dioxide, carnauba wax, microcystalline wax,zein); Colorants (caramel, red, yellow, black or blends, ferric oxide);Complexing agents (ethylenediaminetetraacetic acid and salts (EDTA),edetic acid, gentisic acid ethanolmaide, oxyquinoline sulfate);Desiccants (calcium chloride, calcium sulfate, silicon dioxide);Emulsifying and/or solubilizing agents (acacia, cholesterol,diethanolamine (adjunct), glyceryl monostearate, lanolin alcohols,lecithin, mono- and di-glycerides, monoethanolamine (adjunct), oleicacid (adjunct), oleyl alcohol (stabilizer), poloxamer, polyoxyethylene50 stearate, polyoxyl 35 caster oil, polyoxyl 40 hydrogenated castoroil, polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 40stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate80, propylene glycol diacetate, propylene glycol monostearate, sodiumlauryl sulfate, sodium stearate, sorbitan monolaurate, soritanmonooleate, sorbitan monopalmitate, sorbitan monostearate, stearic acid,trolamine, emulsifying wax); Filtering aids (powdered cellulose,purified siliceous earth); Flavors and perfumes (anethole, benzaldehyde,ethyl vanillin, menthol, methyl salicylate, monosodium glutamate, orangeflower oil, peppermint, peppermint oil, peppermint spirit, rose oil,stronger rose water, thymol, tolu balsam tincture, vanilla, vanillatincture, vanillin); Glidants and/or anticaking agents (calciumsilicate, magnesium silicate, colloidal silicon dioxide, talc);Humectants (glycerin, hexylene glycol, propylene glycol, sorbitol);Plasticizers (castor oil, diacetylated monoglycerides, diethylphthalate, glycerin, mono- and di-acetylated monoglycerides,polyethylene glycol, propylene glycol, triacetin, triethyl citrate);Polymers (e.g., cellulose acetate, alkyl celloloses,hydroxyalkylcelloloses, acrylic polymers and copolymers); Solvents(acetone, alcohol, diluted alcohol, amylene hydrate, benzyl benzoate,butyl alcohol, carbon tetrachloride, chloroform, corn oil, cottonseedoil, ethyl acetate, glycerin, hexylene glycol, isopropyl alcohol, methylalcohol, methylene chloride, methyl isobutyl ketone, mineral oil, peanutoil, polyethylene glycol, propylene carbonate, propylene glycol, sesameoil, water for injection, sterile water for injection, sterile water forirrigation, purified water); Sorbents (powdered cellulose, charcoal,purified siliceous earth); Carbon dioxide sorbents (barium hydroxidelime, soda lime); Stiffening agents (hydrogenated castor oil,cetostearyl alcohol, cetyl alcohol, cetyl esters wax, hard fat,paraffin, polyethylene excipient, stearyl alcohol, emulsifying wax,white wax, yellow wax); Suspending and/or viscosity-increasing agents(acacia, agar, alginic acid, aluminum monostearate, bentonite, purifiedbentonite, magma bentonite, carbomer 934p, carboxymethylcellulosecalcium, carboxymethylcellulose sodium, carboxymethycellulose sodium 12,carrageenan, microcrystalline and carboxymethylcellulose sodiumcellulose, dextrin, gelatin, guar gum, hydroxyethyl cellulose,hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesiumaluminum silicate, methylcellulose, pectin, polyethylene oxide,polyvinyl alcohol, povidone, propylene glycol alginate, silicon dioxide,colloidal silicon dioxide, sodium alginate, tragacanth, xanthan gum);Sweetening agents (aspartame, dextrates, dextrose, excipient dextrose,fructose, mannitol, saccharin, calcium saccharin, sodium saccharin,sorbitol, solution sorbitol, sucrose, compressible sugar, confectioner'ssugar, syrup); Tablet binders (acacia, alginic acid, sodiumcarboxymethylcellulose, microcrystalline cellulose, dextrin,ethylcellulose, gelatin, liquid glucose, guar gum, hydroxypropylmethylcellulose, methycellulose, polyethylene oxide, povidone,pregelatinized starch, syrup); Tablet and/or capsule diluents (calciumcarbonate, dibasic calcium phosphate, tribasic calcium phosphate,calcium sulfate, microcrystalline cellulose, powdered cellulose,dextrates, dextrin, dextrose excipient, fructose, kaolin, lactose,mannitol, sorbitol, starch, pregelatinized starch, sucrose, compressiblesugar, confectioner's sugar); Tablet disintegrants (alginic acid,microcrystalline cellulose, croscarmellose sodium, corspovidone,polacrilin potassium, sodium starch glycolate, starch, pregelatinizedstarch); Tablet and/or capsule lubricants (calcium stearate, glycerylbehenate, magnesium stearate, light mineral oil, polyethylene glycol,sodium stearyl fumarate, stearic acid, purified stearic acid, talc,hydrogenated vegetable oil, zinc stearate); Tonicity agent (dextrose,glycerin, mannitol, potassium chloride, sodium chloride); Vehicle:flavored and/or sweetened (aromatic elixir, compound benzaldehydeelixir, iso-alcoholic elixir, peppermint water, sorbitol solution,syrup, tolu balsam syrup); Vehicle: oleaginous (almond oil, corn oil,cottonseed oil, ethyl oleate, isopropyl myristate, isopropyl palmitate,mineral oil, light mineral oil, myristyl alcohol, octyldodecanol, oliveoil, peanut oil, persic oil, sesame oil, soybean oil, squalane);Vehicle: solid carrier (sugar spheres); Vehicle: sterile (bacteriostaticwater for injection, bacteriostatic sodium chloride injection);Viscosity-increasing (see suspending agent); Water repelling agent(cyclomethicone, dimethicone, simethicone); and Wetting and/orsolubilizing agent (benzalkonium chloride, benzethonium chloride,cetylpyridinium chloride, docusate sodium, nonoxynol 9, nonoxynol 10,octoxynol 9, poloxamer, polyoxyl 35 castor oil, polyoxyl 40,hydrogenated castor oil, polyoxyl 50 stearate, polyoxyl 10 oleyl ether,polyoxyl 20, cetostearyl ether, polyoxyl 40 stearate, polysorbate 20,polysorbate 40, polysorbate 60, polysorbate 80, sodium lauryl sulfate,sorbitan monolaureate, sorbitan monooleate, sorbitan monopalmitate,sorbitan monostearate, tyloxapol). This list is not meant to beexclusive, but instead merely representative of the classes ofexcipients and the particular excipients which may be used in dosageforms of the present invention.

The compounds of the invention can form salts which are also within thescope of this invention. Reference to a compound of the Formula hereinis understood to include reference to salts thereof, unless otherwiseindicated. The term “salt(s)”, as employed herein, denotes acidic saltsformed with inorganic and/or organic acids, as well as basic saltsformed with inorganic and/or organic bases. In addition, when a compoundof the Formulas contains both a basic moiety, such as, but not limitedto a pyridine or imidazole, and an acidic moiety, such as, but notlimited to a carboxylic acid, zwitterions (“inner salts”) may be formedand are included within the term “salt(s)” as used herein.Pharmaceutically acceptable (i.e., non-toxic, physiologicallyacceptable) salts are preferred, although other salts are also useful.Salts of the compounds of the Formulas may be formed, for example, byreacting a compound of Formulas with an amount of acid or base, such asan equivalent amount, in a medium such as one in which the saltprecipitates or in an aqueous medium followed by lyophilization.

Exemplary acid addition salts include acetates, ascorbates, benzoates,benzenesulfonates, bisulfates, borates, butyrates, citrates,camphorates, camphorsulfonates, fumarates, hydrochlorides,hydrobromides, hydroiodides, lactates, maleates, methanesulfonates,naphthalenesulfonates, nitrates, oxalates, phosphates, propionates,salicylates, succinates, sulfates, tartarates, thiocyanates,toluenesulfonates (also known as tosylates) and the like. Additionally,acids which are generally considered suitable for the formation ofpharmaceutically useful salts from basic pharmaceutical compounds arediscussed, for example, by P. Stahl et al, Camille G. (eds.) Handbook ofPharmaceutical Salts. Properties, Selection and Use. (2002) Zurich:Wiley-VCH; S. Berge et al, Journal of Pharmaceutical Sciences (1977)66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33201-217; Anderson et al, The Practice of Medicinal Chemistry (1996),Academic Press, New York; and in The Orange Book (Food & DrugAdministration, Washington, D.C. on their website). These disclosuresare incorporated herein by reference thereto.

Exemplary basic salts include ammonium salts, alkali metal salts such assodium, lithium, and potassium salts, alkaline earth metal salts such ascalcium and magnesium salts, salts with organic bases (for example,organic amines) such as dicyclohexylamines, t-butyl amines, and saltswith amino acids such as arginine, lysine and the like. Basicnitrogen-containing groups may be quarternized with agents such as loweralkyl halides (e.g. methyl, ethyl, and butyl chlorides, bromides andiodides), dialkyl sulfates (e.g. dimethyl, diethyl, and dibutylsulfates), long chain halides (e.g. decyl, lauryl, and stearylchlorides, bromides and iodides), aralkyl halides (e.g. benzyl andphenethyl bromides), and others.

All such acid salts and base salts are intended to be pharmaceuticallyacceptable salts within the scope of the invention and all acid and basesalts are considered equivalent to the free forms of the correspondingcompounds for purposes of the invention.

Pharmaceutically acceptable esters of the compounds of the invention arealso considered to be part of the invention. Pharmaceutically acceptableesters of the present compounds include the following groups: (1)carboxylic acid esters obtained by esterification of the hydroxy groups,in which the non-carbonyl moiety of the carboxylic acid portion of theester grouping is selected from straight or branched chain alkyl (forexample, acetyl, n-propyl, t-butyl, or n-butyl), alkoxyalkyl (forexample, methoxymethyl), aralkyl (for example, benzyl), aryloxyalkyl(for example, phenoxymethyl), aryl (for example, phenyl optionallysubstituted with, for example, halogen, C₁₋₄alkyl, or C₁₋₄alkoxy oramino); (2) sulfonate esters, such as alkyl- or aralkylsulfonyl (forexample, methanesulfonyl); (3) amino acid esters (for example, L-valylor L-isoleucyl); (4) phosphonate esters and (5) mono-, di- ortriphosphate esters. The phosphate esters may be further esterified by,for example, a C₁₋₂₀ alcohol or reactive derivative thereof, or by a2,3-di(C₆₋₂₄)acyl glycerol.

Prodrugs and solvates of the compounds of the invention are alsocontemplated herein. A discussion of prodrugs is provided in T. Higuchiand V. Stella, Pro-drugs as Novel Delivery Systems (1987) 14 of theA.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design,(1987) Edward B. Roche, ed., American Pharmaceutical Association andPergamon Press. The term “prodrug” means a compound (e.g, a drugprecursor) that is transformed in vivo to yield a compound of theinstant Formulas or a pharmaceutically acceptable salt, hydrate orsolvate of the compound. The transformation may occur by variousmechanisms (e.g., by metabolic or chemical processes), such as, forexample, through hydrolysis in blood. A discussion of the use ofprodrugs is provided by T. Higuchi and W. Stella, “Pro-drugs as NovelDelivery Systems,” Vol. 14 of the A.C.S. Symposium Series, and inBioreversible Carriers in Drug Design, ed. Edward B. Roche, AmericanPharmaceutical Association and Pergamon Press, 1987.

For example, if a compound of the instant Formulas or a pharmaceuticallyacceptable salt, hydrate or solvate of the compound contains acarboxylic acid functional group, a prodrug can comprise an ester formedby the replacement of the hydrogen atom of the acid group with a groupsuch as, for example, (C₁-C₅)alkyl, (C₂-C₁₂)alkanoyloxymethyl,1-(alkanoyloxy)ethyl having from 4 to 9 carbon atoms,1-methyl-1-(alkanoyloxy)-ethyl having from 5 to 10 carbon atoms,alkoxycarbonyloxymethyl having from 3 to 6 carbon atoms,1-(alkoxycarbonyloxy)ethyl having from 4 to 7 carbon atoms,1-methyl-1-(alkoxycarbonyloxy)ethyl having from 5 to 8 carbon atoms,N-(alkoxycarbonyl)aminomethyl having from 3 to 9 carbon atoms,1-(N-(alkoxycarbonyl)amino)ethyl having from 4 to 10 carbon atoms,3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl,di-N,N—(C₁-C₂)alkylamino(C₂-C₃)alkyl (such as β-dimethylaminoethyl),carbamoyl-(C₁-C₂)alkyl, N,N-di(C₁-C₂)alkylcarbamoyl-(C₁-C₂)alkyl andpiperidino-, pyrrolidino- or morpholino(C₂-C₃)alkyl, and the like.

Similarly, if a compound of the instant Formulas contains an alcoholfunctional group, a prodrug can be formed by the replacement of thehydrogen atom of the alcohol group with a group such as, for example,(C₁-C₆)alkanoyloxymethyl, 1-((C₁-C₆)alkanoyloxy)ethyl,1-methyl-1-((C₁-C₆)alkanoyloxy)ethyl, (C₁-C₆)alkoxycarbonyloxymethyl,N—(C₁-C₆)alkoxycarbonylaminomethyl, succinoyl, (C₁-C₆)alkanoyl,α-amino(C₁-C₄)alkanyl, arylacyl and α-aminoacyl, orα-aminoacyl-α-aminoacyl, where each α-aminoacyl group is independentlyselected from the naturally occurring L-amino acids, P(O)(OH)₂,—P(O)(O(C₁-C₆)alkyl)₂ or glycosyl (the radical resulting from theremoval of a hydroxyl group of the hemiacetal form of a carbohydrate),and the like.

If a compound of the instant invention incorporates an amine functionalgroup, a prodrug can be formed by the replacement of a hydrogen atom inthe amine group with a group such as, for example, R-carbonyl,RO-carbonyl, NRR′-carbonyl where R and R′ are each independently(C₁-C₁₀)alkyl, (C₃-C₇) cycloalkyl, benzyl, or R-carbonyl is a naturalα-aminoacyl or natural α-aminoacyl, —C(OH)C(O)OY¹ wherein Y¹ is H,(C₁-C₆)alkyl or benzyl, —C(OY²)Y³ wherein Y² is (C₁-C₄) alkyl and Y³ is(C₁-C₆)alkyl, carboxy(C₁-C₆)alkyl, amino(C₁-C₄)alkyl or mono-N— ordi-N,N—(C₁-C₆)alkylaminoalkyl, —C(Y⁴)⁵ wherein Y⁴ is H or methyl and Y⁵is mono-N— or di-N,N—(C₁-C₆)alkylamino morpholino, piperidin-1-yl orpyrrolidin-1-yl, and the like.

One or more compounds of the invention may exist in unsolvated as wellas solvated forms with pharmaceutically acceptable solvents such aswater, ethanol, and the like, and it is intended that the inventionembrace both solvated and unsolvated forms. “Solvate” means a physicalassociation of a compound of this invention with one or more solventmolecules. This physical association involves varying degrees of ionicand covalent bonding, including hydrogen bonding. In certain instancesthe solvate will be capable of isolation, for example when one or moresolvent molecules are incorporated in the crystal lattice of thecrystalline solid. “Solvate” encompasses both solution-phase andisolatable solvates. Non-limiting examples of suitable solvates includeethanolates, methanolates, and the like. “Hydrate” is a solvate whereinthe solvent molecule is H₂O.

One or more compounds of the invention may optionally be converted to asolvate. Preparation of solvates is generally known. Thus, for example,M. Caira et al, J. Pharmaceutical Sci., 93(3), 601-611 (2004) describethe preparation of the solvates of the antifungal fluconazole in ethylacetate as well as from water. Similar preparations of solvates,hemisolvate, hydrates and the like are described by E. C. van Tonder etal, AAPS PharmSciTech., 5(1), article 12 (2004); and A. L. Bingham etal, Chem. Commun., 603-604 (2001). A typical, non-limiting, processinvolves dissolving the inventive compound in desired amounts of thedesired solvent (organic or water or mixtures thereof) at a higher thanambient temperature, and cooling the solution at a rate sufficient toform crystals which are then isolated by standard methods. Analyticaltechniques such as, for example I. R. spectroscopy, show the presence ofthe solvent (or water) in the crystals as a solvate (or hydrate).

Compounds of the invention, and salts, solvates, esters and prodrugsthereof may exist in their tautomeric form (for example, as an amide orimino ether). All such tautomeric forms are contemplated herein as partof the present invention.

The compounds of the invention may contain asymmetric or chiral centers,and, therefore, exist in different stereoisomeric forms. It is intendedthat all stereoisomeric forms of the compounds of the various Formulasas well as mixtures thereof, including racemic mixtures, form part ofthe present invention. In addition, the present invention embraces allgeometric and positional isomers. For example, if a compound of thevarious Formulas incorporates a double bond or a fused ring, both thecis- and trans-forms, as well as mixtures, are embraced within the scopeof the invention.

Diastereomeric mixtures can be separated into their individualdiastereomers on the basis of their physical chemical differences bymethods well known to those skilled in the art, such as, for example, bychromatography and/or fractional crystallization. Enantiomers can beseparated by converting the enantiomeric mixture into a diastereomericmixture by reaction with an appropriate optically active compound (e.g.,chiral auxiliary such as a chiral alcohol or Mosher's acid chloride),separating the diastereomers and converting (e.g., hydrolyzing) theindividual diastereomers to the corresponding pure enantiomers. Also,some of the compounds of the various Formulas may be atropisomers (e.g.,substituted biaryls) and are considered as part of this invention.Enantiomers can also be separated by use of chiral HPLC column.

It is also possible that the compounds of the various Formulas may existin different tautomeric forms, and all such forms are embraced withinthe scope of the invention. Also, for example, all keto-enol andimine-enamine forms of the compounds are included in the invention.

All stereoisomers (for example, geometric isomers, optical isomers andthe like) of the present compounds (including those of the salts,solvates, esters and prodrugs of the compounds as well as the salts,solvates and esters of the prodrugs), such as those which may exist dueto asymmetric carbons on various substituents, including enantiomericforms (which may exist even in the absence of asymmetric carbons),rotameric forms, atropisomers, and diastereomeric forms, arecontemplated within the scope of this invention, as are positionalisomers (such as, for example, 4-pyridyl and 3-pyridyl). (For example,if a compound of the various Formulas incorporates a double bond or afused ring, both the cis- and trans-forms, as well as mixtures, areembraced within the scope of the invention. Also, for example, allketo-enol and imine-enamine forms of the compounds are included in theinvention.) Individual stereoisomers of the compounds of the inventionmay, for example, be substantially free of other isomers, or may beadmixed, for example, as racemates or with all other, or other selected,stereoisomers. The chiral centers of the present invention can have theS or R configuration as defined by the IUPAC 1974 Recommendations. Theuse of the terms “salt”, “solvate”, “ester”, “prodrug” and the like, isintended to equally apply to the salt, solvate, ester and prodrug ofenantiomers, stereoisomers, rotamers, tautomers, positional isomers,racemates or prodrugs of the inventive compounds.

The present invention also embraces isotopically-labelled compounds ofthe present invention which are identical to those recited herein, butfor the fact that one or more atoms are replaced by an atom having anatomic mass or mass number different from the atomic mass or mass numberusually found in nature. Examples of isotopes that can be incorporatedinto compounds of the invention include isotopes of hydrogen, carbon,nitrogen, oxygen, phosphorus, fluorine and chlorine, such as ²H, ³H,¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ³¹P, ³²P, ³⁵S, ¹⁸F, and ³⁶Cl, respectively.

Certain isotopically-labelled compounds of the various Formulas (e.g.,those labeled with ³H and ¹⁴C) are useful in compound and/or substratetissue distribution assays. Tritiated (i.e., ³H) and carbon-14 (i.e.,¹⁴C) isotopes are particularly preferred for their ease of preparationand detectability. Further, substitution with heavier isotopes such asdeuterium (i.e., ²H) may afford certain therapeutic advantages resultingfrom greater metabolic stability (e.g., increased in vivo half-life orreduced dosage requirements) and hence may be preferred in somecircumstances. Isotopically labelled compounds of the various Formulascan generally be prepared by following procedures analogous to thosedisclosed in the Schemes and/or in the Examples hereinbelow, bysubstituting an appropriate isotopically labelled reagent for anon-isotopically labelled reagent.

Polymorphic forms of the compounds of the invention, and of the salts,solvates, esters and prodrugs of the compounds of the invention, areintended to be included in the present invention.

Benefits of the present invention include oral administration of anoptimal amount of a nicotinamide phosphoribosyltransferase biosynthesisinhibitor.

Benefits of the present invention include intravenous administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intraperitoneal administrationof an optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intramural administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intramuscular administrationof an optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include subcutaneous administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intra-tumor administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intrathecal administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include subdural administration of anoptimal amount of a nicotinamide phosphoribosyltransferase biosynthesisinhibitor.

Benefits of the present invention include periorbital administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Based on these results, the present invention has important implicationsfor the design of novel treatment strategies for patients with cancer,including leukemias and solid tumors, inflammatory diseases,osteoporosis, atherosclerosis; irritable bowel syndrome and otherconditions disclosed herein or that are known to those skilled in theart.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

An aspect of the present invention concerns compounds disclosed herein.

An aspect of the present invention concerns compounds which are or canbe inhibitors of the formation of nicotinamidephosphoribosyltransferase.

An aspect of the present invention concerns the use of an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment, prevention,inhibition or elimination of tumors.

An aspect of the present invention concerns the use of an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment, prevention,inhibition or elimination of cancer. An aspect of the present inventionconcerns the use of an inhibitor of the formation of nicotinamidephosphoribosyltransferase for the preparation of a medicament used inthe treatment, prevention, inhibition or elimination of cancer, wherethe cancer is selected from leukemia, lymphoma, ovarian cancer, breastcancer, uterine cancer, colon cancer, cervical cancer, lung cancer,prostate cancer, skin cancer, CNS cancer, bladder cancer, pancreaticcancer and Hodgkin's disease.

The present invention also describes one or more methods of synthesizingthe compounds of the present invention.

The invention also describes one or more uses of the compounds of thepresent invention.

The invention also describes one or more uses of the compounds of thepresent invention with an adjunctive agent such as use with TNF, GCSF,or other chemotherapeutic agents The invention also describes one ormore uses of the pharmaceutical compositions of the present invention.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of inflammatorydiseases.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of inflammatorydiseases, such as Irritable Bowel Syndrome or Inflammatory BowelDisease.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of disease of the bonesuch as osteoporosis.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of disease of thecardiovascular system, such as atherosclerosis.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of disease or acondition caused by an elevated level of NAMPT.

Such disease or condition is one or more selected from the groupconsisting of cancer, ovarian cancer, breast cancer, uterine cancer,colon cancer, cervical cancer, lung cancer, prostate cancer, skincancer, bladder cancer, pancreatic cancer, leukemia, lymphoma, Hodgkin'sdisease, viral infections, Human Immunodeficiency Virus, hepatitisvirus, herpes virus, herpes simplex, inflammatory disorders, irritablebowel syndrome, inflammatory bowel disease, rheumatoid arthritis,asthma, chronic obstructive pulmonary disease, osteoarthritis,osteoporosis, dermatitis, atoptic dermatitis, psoriasis, systemic lupuserythematosis, multiple sclerosis, psoriatic arthritis, ankylosingspodylitis, graft-versus-host disease, Alzheimer's disease,cerebrovascular accident, atherosclerosis, diabetes,glomerulonephiritis, metabolic syndrome, non-small cell lung cancer,small cell lung cancer, multiple myeloma, leukemias, lymphomas, squamouscell cancers, kidney cancer, uretral and bladder cancers, cancers ofhead and neck, cancers of the brain and central nervous system (CNS).

The compounds of the invention can be useful in the therapy ofproliferative diseases such as cancer, autoimmune diseases, viraldiseases, fungal diseases, neurological/neurodegenerative disorders,arthritis, inflammation, anti-proliferative (e.g., ocular retinopathy),neuronal, alopecia and cardiovascular disease.

More specifically, the compounds can be useful in the treatment of avariety of cancers, including (but not limited to) the following:carcinoma, including that of the bladder, breast, colon, kidney, liver,lung, including small cell lung cancer, non-small cell lung cancer, headand neck, esophagus, gall bladder, ovary, pancreas, stomach, cervix,thyroid, prostate, and skin, including squamous cell carcinoma;hematopoietic tumors of lymphoid lineage, including leukemia, acutelymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma,T-cell lymphoma, Hodgkins lymphoma, non-Hodgkins lymphoma, hairy celllymphoma, mantle cell lymphoma, myeloma, and Burkett's lymphoma;hematopoietic tumors of myeloid lineage, including acute and chronicmyelogenous leukemias, myelodysplastic syndrome and promyelocyticleukemia;

tumors of mesenchymal origin, including fibrosarcoma andrhabdomyosarcoma; tumors of the central and peripheral nervous system,including astrocytoma, neuroblastoma, glioma and schwannomas; and othertumors, including melanoma, seminoma, teratocarcinoma, osteosarcoma,xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer andKaposi's sarcoma.

The compounds of the invention may induce or inhibit apoptosis.

The compounds of the invention may also be useful in the chemopreventionof cancer. Chemoprevention is defined as inhibiting the development ofinvasive cancer by either blocking the initiating mutagenic event or byblocking the progression of pre-malignant cells that have alreadysuffered an insult or inhibiting tumor relapse.

A further aspect of the invention is a method of inhibiting a NAMPTpathway in an animal, said method comprising administering to saidanimal a pharmaceutically acceptable amount of a compound of theinvention to an animal in need thereof.

A further aspect of the invention is a pharmaceutical formulationcomprising a compound of the invention.

Another embodiment of the invention comprises a pharmaceuticalformulation of the invention, wherein the pharmaceutical formulation,upon administration to a human, results in a decrease in tumor burden.

Still another embodiment of the invention is a pharmaceuticalformulation, further comprising one or more of an antineoplastic agent,a chemotherapeutic agent, or an adjunctive chemotherapeutic agent.

The pharmaceutical formulations of the invention may further comprise atherapeutic effective amount of an adjunctive chemotherapeutic agent.

The adjunctive chemotherapeutic agent may be an agent, which modifiesblood cell growth and maturation. Non-limiting examples of adjunctivechemotherapeutic agent are filgrastim, pegfilgrastim and erythropoietin.

The invention is also directed to a method of treating or preventing adisorder associated with excessive rate of growth of cells in a mammalcomprising administering to the mammal an effective amount of thepharmaceutical formulation of the invention. Non-limiting examples ofdisorder include cancer or metastasis from malignant tumors.

Another aspect of the invention is a method of inhibiting tumor cellgrowth and rate of division in a mammal with cancer, or other disorderassociated with abnormally dividing cells comprising administering tothe mammal an effective amount of the pharmaceutical formulation of thisinvention.

Another embodiment of the invention is a method of treating bone paindue to excessive growth of a tumor or metastasis to bone in a mammal inneed thereof comprising administering to the mammal an effective amountof the pharmaceutical formulation of this invention.

Still another embodiment of the invention is a method for administeringa NAMPT-inhibitor-containing compound to a mammal in need thereofcomprising administering to the mammal the pharmaceutical formulation ofthe invention. In one embodiment, the mammal is a human.

A further embodiment of the invention is a method of preparing apharmaceutical formulation comprising mixing at least onepharmaceutically acceptable compound of the present invention, and,optionally, one or more pharmaceutically acceptable excipients oradditives.

The invention is also directed to methods of synthesizing compounds ofthe present invention.

Compounds of the Invention

The invention is directed to pharmaceutical compositions comprising oneor more compounds as described herein and pharmaceutically acceptablesalts, solvates, esters, prodrugs or isomers thereof. The inventionfurther relates to molecules which are useful in inhibiting the enzymenicotinamide phosphoribosyltransferase (NAMPT) and pharmaceuticallyacceptable salts, solvates, esters, prodrugs or isomers thereof.

An aspect of the invention is the provision of compounds, compositions,kits, and antidotes for the NAMPT pathway in mammals having a compoundof Formula I

wherein

-   Ar¹ is aryl, heteroaryl or heterocycloalkyl, wherein the heteroatom    of each of said heteroaryl and heterocycloalkyl numbers 1, 2 or 3,    and is independently selected from N, S or O, further wherein each    of said aryl, heteroaryl and heterocycloalkyl may independently be    either substituted or fused with aryl, heteroaryl or    heterocycloalkyl, still further wherein any of said aryl, heteroaryl    and heterocycloalkyl is either unsubstituted or optionally    independently substituted with one or more substituents which can be    the same or different and are independently selected from the group    consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z),    alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-,    (alkoxyalkyl)amino-, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl,    —N(R³)—C(O)—O— alkyl, —N(R³)—C(O)—O-aryl, -cycloalkyl,    -heterocycloalkyl, -aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl,    with the proviso that no two adjacent ring heteroatoms are both S or    both O;-   X is a straight or branched C₁-C₆ alkyl;-   L is selected from NHC(O)NH, OC(O)NH, NHC(O)O, OCH₂C(O)NH, C(O)NH,    NHC(S)NH, OC(S)NH, NHC(S)O, OCH₂C(S)NH, or C(S)NH;-   A is aryl, heteroaryl, heterocycloalkyl or C₃ to C₈ cycloalkyl, with    each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl being    either unsubstituted or optionally independently substituted with 1,    2, 3 or 4 substituents which can be the same or different and are    independently selected from the group consisting of deuterium, halo,    cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂,    —C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂,    —CH_(z)F_(3-z), —OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, alkoxy-,    -aryloxy-, (alkoxyalkyl)oxy-, (alkoxyalkyl)amino-,    —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —N(R³)—C(O)—O-alkyl,    —N(R³)—C(O)—O-aryl, -cycloalkyl, -heterocycloalkyl,-aryl,    —C(O)-aryl, —S(O)-aryl, and heteroaryl;-   Q is C(O), S(O), S(O)₂;-   R³ is H, alkyl or arylalkyl-;-   z is 0, 1 or 2; and    either:    -   (i) (a) R¹ is selected from H, a straight or branched C₁ to C₇        alkyl, straight or branched C₁ to C₇ alkoxy, straight or        branched C₁ to C₄ hydroxyalkyl, aryl, heteroaryl,        heterocycloalkyl, cycloalkyl, arylalkyl-, heteroarylalkyl-,        heterocycloalkylalkyl-, cycloalkylalkyl-, hydroxyalkyl-,        alkoxyalkyl-, heterospirocycloalkyl and        heterospiroheterocycloalkyl, wherein the heteroatoms of said        heteroaryl and heterocycloalkyl in the moieties above are        independently selected from one or more N, O and S, with the        proviso that no two adjacent ring heteroatoms are both S or both        O, further wherein R¹ can be either unsubstituted or optionally        independently (i) either substituted with one or more        substituents which can be the same or different and are        independently selected from the group consisting of deuterium,        halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-,        —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl),        —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z), alkyl, alkenyl,        alkynyl, hydroxyalkyl-, (hydroxyalkyl)oxy, -alkoxy, carboxy,        (alkoxyalkyl)-, (heteroaryloxy)alkyl-, —NO₂,        (alkoxyalkyl)amino-, -alkylamino, dialkylamino,        (heterocycloalkyloxo)alkyl-, aryloxy, heterocycloalkyloxy-,        aminocarbonyl-, —CHO, —C(O)alkyl, —N(R³)—C(O)-alkyl,        —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃, -cycloalkyl,        alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl,-aryl,        and heteroaryl, or (ii) fused with a cycloalkyl,        -heterocycloalkyl,-aryl, or heteroaryl; and (b) R² is selected        from H, a straight or branched C₁ to C₇ alkyl, straight or        branched C₁ to C₇ alkoxy, straight or branched C₁ to C₄        hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl,        arylalkyl-, heteroarylalkyl-, heterocycloalkylalkyl-,        cycloalkylalkyl-, hydroxyalkyl-, alkoxyalkyl-,        heterospirocycloalkyl and heterospiroheterocycloalkyl, wherein        the heteroatoms of said heteroaryl and heterocycloalkyl in the        moieties above are independently selected from one or more N, O        and S, with the proviso that no two adjacent ring heteroatoms        are both S or both O, further wherein R² can be either        unsubstituted or optionally independently (i) either substituted        with one or more substituents which can be the same or different        and are independently selected from the group consisting of        deuterium, halo, cyano, isocyano, amino, aminoalkyl-,        (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,        —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z),        alkyl, alkenyl, alkynyl, hydroxyalkyl-,        (hydroxyalkyl)oxy,-alkoxy, carboxy, (alkoxyalkyl)-,        (heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,        dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,        heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,        —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,        -cycloalkyl, alkylenedioxy (e.g, methylenedioxy),        -heterocycloalkyl, -aryl, and heteroaryl, or (ii) fused with a        cycloalkyl, -heterocycloalkyl, -aryl, or heteroaryl;-   or (ii) R¹ and R² are joined together to form, along with the N they    are shown attached to in the formula, a C₃-C₈ heterocycloalkyl, a    C₃-C₅ heterocycloalkenyl, a fused bicyclic heterocycloalkyl, a fused    tricyclic heterocycloalkyl, spiroheterocycloalkyl or a    heterospiroheterocycloalkyl, wherein each of said heterocycloalkyl,    heterocycloalkenyl, spiroheterocycloalkyl and    heterospiroheterocycloalkyl can optionally contain one or more    heteroatoms in addition to the N atom they are shown attached to in    the formula, said heteroatoms being selected from N, S and O, with    the proviso that no two adjacent ring heteroatoms are both S or both    O, further wherein each of said heterocycloalkyl, fused bicyclic    heterocycloalkyl, fused tricyclic heterocycloalkyl,    heterocycloalkenyl, spiroheterocycloalkyl and    heterospiroheterocycloalkyl can be either unsubstituted or    optionally independently substituted with one or more substituents    which can be the same or different and are independently selected    from the group consisting of deuterium, halo, cyano, isocyano,    amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),    —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z),    —OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, hydroxyalkyl-,    (hydroxyalkyl)oxy,-alkoxy, carboxy, (alkoxyalkyl)-,    (heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,    dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,    heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,    —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,    -cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl,    -aryl, and heteroaryl;    and pharmaceutically acceptable salts, solvates, esters and isomers    thereof, with the proviso that the compound of Formula I is not    1-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea,    3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea    or    3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

Another aspect of this invention is the provision of compounds,compositions, kits, and antidotes for the NAMPT pathway in mammalshaving a compound of the Formula I, where X,L,Q, Ar^(t) and A are asdefind in Formula I and R¹ is selected from H, a straight or branched C₁to C₇ alkyl, straight or branched C₁ to C₇ alkoxy, straight or branchedC₁ to C₄ hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl,arylalkyl-, heteroarylalkyl-, heterocycloalkylalkyl-, cycloalkylalkyl-,hydroxyalkyl-, alkoxyalkyl-, spiroheterocycloalkyl andheterospiroheterocycloalkyl, wherein the heteroatoms of said heteroaryland heterocycloalkyl in the moieties above are independently selectedfrom one or more N, O and S, with the proviso that no two adjacent ringheteroatoms are both S or both O, further wherein R¹ can be eitherunsubstituted or optionally independently (i) either substituted withone or more substituents which can be the same or different and areindependently selected from the group consisting of deuterium, halo,cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂,—C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂,—CH_(z)F_(3-z), —OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, hydroxyalkyl-,(hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-,(heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,—N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,-cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl,-aryl, and heteroaryl, or (ii) fused with a cycloalkyl,-heterocycloalkyl, -aryl, or heteroaryl; and

R² is selected from H, a straight or branched C₁ to C₇ alkyl, straightor branched C₁ to C₇ alkoxy, straight or branched C₁ to C₄ hydroxyalkyl,aryl, heteroaryl, heterocycloalkyl, cycloalkyl, arylalkyl-,heteroarylalkyl-, heterocycloalkylalkyl-, cycloalkylalkyl-,hydroxyalkyl-, alkoxyalkyl-, heterospirocycloalkyl andheterospiroheterocycloalkyl, wherein the heteroatoms of said heteroaryland heterocycloalkyl in the moieties above are independently selectedfrom one or more N, O and S, with the proviso that no two adjacent ringheteroatoms are both S or both O, further wherein R² can be eitherunsubstituted or optionally independently (i) either substituted withone or more substituents which can be the same or different and areindependently selected from the group consisting of deuterium, halo,cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂,—C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂,—CH_(z)F_(3-z), —OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, hydroxyalkyl-,(hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-,(heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,—N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,-cycloalkyl, alkylenedioxy (e.g, methylenedioxy),-heterocycloalkyl,-aryl, and heteroaryl, or (ii) fused with acycloalkyl, -heterocycloalkyl,-aryl, or heteroaryl;

with the proviso that the compound of Formula I is not1-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea,3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea or3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

Another aspect of this invention is the provision of compounds,compositions, kits, and antidotes for the NAMPT pathway in mammalshaving a compound of the Formula I, where X,L,Q, Ar¹ and A are as defindin Formula I and R¹ and R² are joined together to form, along with the Nthey are shown attached to in the formula, a C₃-C₈ heterocycloalkyl, aC₃-C₈ heterocycloalkenyl, a fused bicyclic heterocycloalkyl, a fusedtricyclic heterocycloalkyl, spiroheterocyclaolkyl or aheterospiroheterocycloalkyl, wherein each of said heterocycloalkyl,heterocycloalkenyl, spiroheterocyclaolkyl andheterospiroheterocycloalkyl can optionally contain one or moreheteroatoms in addition to the N atom they are shown attached to in theformula, said heteroatoms being selected from N, S and O, with theproviso that no two adjacent ring heteroatoms are both S or both O,further wherein each of said heterocycloalkyl, fused bicyclicheterocycloalkyl, fused tricyclic heterocycloalkyl, heterocycloalkenyl,spiroheterocyclaolkyl and heterospiroheterocycloalkyl can be eitherunsubstituted or optionally independently substituted with one or moresubstituents which can be the same or different and are independentlyselected from the group consisting of deuterium, halo, cyano, isocyano,amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),—C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z),—OCH_(z)F_(3-z), alkyl, alkenyl, alkynyl, hydroxyalkyl-,(hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-,(heteroaryloxy)alkyl-, —NO₂, (alkoxyalkyl)amino-, -alkylamino,dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy,heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl,—N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)alkyl, —S(O₂)CF₃,-cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl,-aryl, and heteroaryl;

R³ is H, alkyl or arylalkyl with the proviso that the compound is not1-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea,3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea or3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

In one embodiment, the invention relates to compounds of Formula I andpharmaceutically acceptable salts, solvates, ester or isomers thereof.

In the compounds of Formula I, the various moieties and substituents areindependently selected.

The following embodiments are directed to Formula I as applicable.Further, the moieties aryl, heteroaryl, heterocycloalkyl, cycloalkyl,spiroheterocycloalkyl and heterospiroheterocycloalkyl as well as theirrepresentative moieties in these embodiments can be independentlyunsubstituted or optionally substituted or optionally fused as describedearlier. Any one or more of the embodiments relating to Formula I belowcan be combined with one or more other embodiments of Formula I.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹ is aryl,and z, X, L, A, Q, R, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹ isheteroaryl, and z, X, L, A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹ isheterocycloalkyl, and z, X, L, A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹ is arylfused with an aryl, heteroaryl or heterocycloalkyl, and z, X, L, A, Q,R, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹ isheteroaryl fused with an aryl, heteroaryl or heterocycloalkyl, and z, X,L, A, Q, R, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹ isheterocycloalkyl fused with an aryl, heteroaryl or heterocycloalkyl, andz, X, L, A, Q, R, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹ is arylsubstituted as shown under Formula I, IA or IB, and z, X, L, A, Q, R¹,R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹ isheteroaryl substituted as shown under Formula I, IA or IB, and z, X, L,A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹ isheterocycloalkyl substituted as shown under Formula I, IA or IB, and z,X, L, A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, X is astraight chain alkyl, and Ar¹, z, L, A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, X is abranched chain alkyl, and Ar¹, z, L, A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, L is—N(H)—C(O)—N(H)—, and Ar¹, z, X, A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Q is —S(O₂)—,and Ar¹, z, X, A, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R³ is H, andAr¹, z, X, A, Q, R¹, and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R³ is alkyl,and Ar¹, z, X, A, Q, R¹, and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R³ isarylalkyl, and Ar¹, z, X, A, Q, R¹, and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, z is 0, andAr¹, X, A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, z is 1, andAr¹, X, A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, z is 2, andAr¹, X, A, Q, R¹, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, andAr¹, z, X, A, Q, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R² is H, andAr¹, z, X, A, Q, R² and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² areH, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isaryl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isheteroaryl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isheterocycloalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² iscycloalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isalkoxy, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² ishydroxyalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isaryloxy, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isarylalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isheteroarylalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² iscycloalkylalkyl-, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isheterocycloalkylalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isalkoxyalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isspiroheterocycloalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isspiroheterocycloalkylalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isalkyl substituted or fused as described earlier, and Ar¹, z, X, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isaryl substituted or fused as described earlier, and Ar¹, z, X, A, Q, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isheteroaryl substituted or fused as described earlier, and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isheterocycloalkyl substituted or fused as described earlier, and Ar¹, z,X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² iscycloalkyl substituted or fused as described earlier, and Ar¹, z, X, A,Q, and R³ are as defined. An embodiment of the invention is theprovision of a compound of Formula I, where the various moieties areindependently selected, R¹ is H, R² is aryloxy with the aryl substitutedor fused as described earlier, and Ar¹, z, X, A, Q, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isarylalkyl with the aryl substituted or fused as described earlier, andAr¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isheteroarylalkyl with the heteroaryl substituted or fused as describedearlier, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² iscycloa-kylalkyl-with the cycloalkyl substituted or fused as describedearlier, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isheterocycloalkylalkyl with the heterocycloalkyl substituted or fused asdescribed earlier, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isspiroheterocycloalkyl substituted or fused as described earlier, and Ar,z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isspiroheterocycloalkylalkyl substituted or fused as described earlier,and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is alkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is aryl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is heteroaryl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is heterocycloalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is cycloalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is aryloxy, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is arylalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is heteroarylalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is cycloalkylalkyl-, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is heterocycloalkylalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is spiroheterocycloalkyl, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is spiroheterocycloalkylalkyl, and Ar¹, z, X, A, Q, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is alkyl substituted or fused as described earlier, and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is aryl substituted or fused as described earlier, and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is heteroaryl substituted or fused as described earlier, and Ar¹, z,X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is heterocycloalkyl substituted or fused as described earlier, andAr¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is cycloalkyl substituted or fused as described earlier, and Ar¹, z,X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is aryloxy with the aryl substituted or fused as described earlier,and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is arylalkyl with the aryl substituted or fused as described earlier,and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is heteroarylalkyl with the heteroaryl substituted or fused asdescribed earlier, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is cycloalkylalkyl-with the cycloalkyl substituted or fused asdescribed earlier, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is heterocycloalkylalkyl with the heterocycloalkyl substituted orfused as described earlier, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is spiroheterocycloalkyl substituted or fused as described earlier,and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is alkyl,R² is spiroheterocycloalkylalkyl substituted or fused as describedearlier, and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isbicycloheptanyl (unsubstituted, substituted or fused as describedearlier), and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² iscyclopropyl (unsubstituted, substituted or fused as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² iscyclobutyl (unsubstituted, substituted or fused as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² iscyclopentyl (unsubstituted, substituted or fused as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² iscyclopentylmethyl (unsubstituted, substituted or fused as describedearlier), and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isbenzyl (unsubstituted, substituted or fused as described earlier), andAr¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isfuranyl (unsubstituted, substituted or fused as described earlier), andAr¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isfuranylmethyl (unsubstituted, substituted or fused as describedearlier), and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isphenyl (unsubstituted, substituted or fused as described earlier), andAr¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isnaphthalenyl (unsubstituted, substituted or fused as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isbiphenylmethyl (unsubstituted, substituted or fused as describedearlier), and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isbiphenyl (unsubstituted, substituted or fused as described earlier), andAr¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² istolyl (unsubstituted, substituted or fused as described earlier), andAr¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² ispyridinyl (unsubstituted, substituted or fused as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isunsubstituted, pyridinylmethyl (substituted or fused as describedearlier), and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isphenylethyl (unsubstituted, substituted or fused as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is benzyl(unsubstituted, substituted or fused as described earlier), R² is benzyl(unsubstituted, substituted or fused as described earlier), and Ar¹, z,X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isquinolinyl (unsubstituted, substituted or fused as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isoxazolyl (unsubstituted, substituted or fused as described earlier), andAr¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isindazolyl (unsubstituted, substituted or fused as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isdihydrobenzodioxepinyl (unsubstituted, substituted or fused as describedearlier), and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² ispyrazolyl (unsubstituted, substituted or fused as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isterrahydronaphthalenyl (unsubstituted, substituted or fused as describedearlier), and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isisoquinolinyl (unsubstituted, substituted or fused as describedearlier), and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ is H, R² isoxolanyl (unsubstituted, substituted or fused as described earlier), andAr¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a heterocycloalkyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a heterocycloalkenyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a fused bicyclicheterocycloalkyl (unsubstituted or substituted as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a fused tricyclicheterocycloalkyl (unsubstituted or substituted as described earlier),and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a spiroheterocycloalkyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a heterospiroheterocycloalkyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a piperidinyl (unsubstitutedor substituted as described earlier), and Ar¹, z, X, A, Q, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a piperazinyl (unsubstitutedor substituted as described earlier), and Ar¹, z, X, A, Q, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a morpholinyl (unsubstitutedor substituted as described earlier), and Ar¹, z, X, A, Q, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, an azapenyl (unsubstituted orsubstituted as described earlier), and Ar¹, z, X, A, Q, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, an azetidinyl (unsubstitutedor substituted as described earlier), and Ar¹, z, X, A, Q, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a oxaazabicyclooctanyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, an azabicycloheptanyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a dihydrobenzoxazinyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a dihydroindolyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a thiomorpholinyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, anazatricyclotridecapentaenyl (unsubstituted or substituted as describedearlier), and Ar¹, z, X, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, an azaspirodecanyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a terrahydronaphthyridinyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, an azabicyclooctanyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a diazepanyl (unsubstitutedor substituted as described earlier), and Ar¹, z, X, A, Q, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a decahydroquinolyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a diazaspiroundecanyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R¹ and R² arejoined together to form, along with the N, a terahydroisoquinolinyl(unsubstituted or substituted as described earlier), and Ar¹, z, X, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹, z, X, A,Q, and R³ are as defined, and R¹ and R² are the same or different,wherein said R¹ and R² independently are unsubstituted or substitutedwith one or more substituents which can be the same or different and areindependently selected from the group consisting of —C(O)NH₂, alkyl,—C(O)NH(alkyl), —C(O)N(alkyl)₂, halo, morpholinyl, alkoxyalkyl-,alkenyl, alkyl, CF₃, OH, CN, phenyl, isocyano, —N(H)C(O)CH₃,phenylethyl-, —C(O)CH₃, phenoxy, —S(O₂)CH₃, —S(O₂)CF₃, pyrazinyl,—OCHF₂, OCF₃, OCH₂F, —C≡CH, —CH═CH₂, methylenedioxy, ethylenedioxy,benzyloxy, piperidinyl, —C(O)O—CH₃, phenoxy, oxopiperazinyl,oxopyrrolidinylmethyl-, NH2, NH(alkyl, —N(alkyl)₂, morpholinyloxoethyl-,oxopyrrolinylmethyl-, azapanyl, nitrophenyl-, cyclopropyl,hydroxymethyl-, (hydroxyalkyl)oxy-, isopropyl, ethyl, methyl andphenylpropenyl-.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar¹, z, X, A,Q, and R³ are as defined, and R¹ and R² are joined together to form,along with the N, a C₃-C₈ heterocycloalkyl, a C₃-C₈ heterocycloalkenyl,a fused bicyclic heterocycloalkyl, a fused tricyclic heterocycloalkyl,spiroheterocycloalkyl or a heterospiroheterocycloalkyl, wherein each ofsaid C₃-C₈ heterocycloalkyl, a C₃-C₈ heterocycloalkenyl, a fusedbicyclic heterocycloalkyl, a fused tricyclic heterocycloalkyl,spiroheterocycloalkyl or a heterospiroheterocycloalkyl independently isunsubstituted or bears one or more substituents which can be the same ordifferent and are independently selected from the group consisting of—C(O)NH₂, alkyl, —C(O)NH(alkyl), —C(O)N(alkyl)₂, halo, morpholinyl,alkoxyalkyl-, alkenyl, alkyl, CF₃, OH, CN, phenyl, isocyano,—N(H)C(O)CH₃, phenylethyl-, —C(O)CH₃, phenoxy, —S(O₂)CH₃, —S(O₂)CF₃,pyrazinyl, —OCHF₂, OCF₃, OCH₂F, —C≡CH, —CH═CH₂, methylenedioxy,ethylenedioxy, benzyloxy, piperidinyl, —C(O)O—CH₃, phenoxy,oxopiperazinyl, oxopyrrolidinylmethyl-, NH2, NH(alkyl, —N(alkyl)₂,morpholinyloxoethyl-, oxopyrrolinylmethyl-, azapanyl, nitrophenyl-,cyclopropyl, hydroxymethyl-, (hydroxyalkyl)oxy-, isopropyl, ethyl,methyl and phenylpropenyl-.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, R² is aryl, and z, X, L, A, Q, and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, R² is heteroaryl, and z, X, L, A, Q, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, R² is heterocycloalkyl, and z, X, L, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, R² is spiroheterocycloalkyl, and z, X,L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, R² is heterospiroheterocycloalkyl, andz, X, L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is aryl, and z, X, L, A, Q, andR³ are as defined.

An embodiment of the invention is the provision of a compound of Formulawhere NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is heteroaryl, and z, X, L, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is heterocycloalkyl, and z, X,L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is spiroheterocycloalkyl, andz, X, L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is heterospiroheterocycloalkyl,and z, X, L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, R² is aryl, A is phenyl, and z, X, L, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, A is phenyl, R² is heteroaryl, and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, A is phenyl, R² is heterocycloalkyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, A is phenyl, R² isspiroheterocycloalkyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is aryl, R¹ is H, A is phenyl, R² isheterospiroheterocycloalkyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is aryl, A is phenyl, and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of Formulawhere NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is heteroaryl, A is phenyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is heterocycloalkyl, and z, X,L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of Formulawhere NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is spiroheterocycloalkyl, A isphenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is heterospiroheterocycloalkyl,A is phenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is phenyl, R¹ is H, R² is aryl, A is phenyl, and z, X, L,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is phenyl, R¹ is H, A is phenyl, R² is heteroaryl, and z,X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is phenyl, R¹ is H, A is phenyl, R² is heterocycloalkyl,and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is phenyl, R¹ is H, A is phenyl, R² isspiroheterocycloalkyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is phenyl, R¹ is H, A is phenyl, R² isheterospiroheterocycloalkyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is aryl, A is phenyl, and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is heteroaryl, A is phenyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is heterocycloalkyl, and z, X,L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is spiroheterocycloalkyl, A isphenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, R¹ is H, R² is heterospiroheterocycloalkyl,A is phenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridyl, R¹ is H, R² is aryl, A is phenyl, and z, X, L,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridyl, R¹ is H, R² is heteroaryl, A is phenyl, and z,X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of Formulawhere NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridyl, R¹ is H, R² is heterocycloalkyl, and z, X, L,A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridyl, R¹ is H, R² is spiroheterocycloalkyl, A isphenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridyl, R¹ is H, R² is heterospiroheterocycloalkyl, Ais phenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is piperidinyl, R¹ is H, R² is aryl, A is phenyl, and z,X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is piperidinyl, R¹ is H, R² is heteroaryl, A is phenyl,and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is piperidinyl, R¹ is H, R² is heterocycloalkyl, and z, X,L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is piperidinyl, R¹ is H, R² is spiroheterocycloalkyl, A isphenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of Formulawhere NR R² is acyclic, where the various moieties are independentlyselected, Ar is piperidinyl, R¹ is H, R² is heterospiroheterocycloalkyl,A is phenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is piperidinyl, R¹ is H, R² is pyrrolyl, A is phenyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is piperidinyl, R¹ is H, R² is pyrrolyl, A is phenyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is piperidinyl, R¹ is H, R² is pyridinylmethyl, and z, X,L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is pyrrolyl, A is phenyl, and z,X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is piperidinyl, R¹ is H, R² is pyrrolyl, A is phenyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is pyridinylmethyl, and z, X, L,A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is alkyl, A is phenyl, and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is hydroxyalkyl, A is phenyl,and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is phenylalkyl, A is phenyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is cycloalkyl, A is phenyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is oxolanyl, A is phenyl, and z,X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is quinolinyl, A is phenyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is oxazolyl, A is phenyl, and z,X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is spiroheterocycloakyl, A isphenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is heterospiroheterocycloalkyl,A is phenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is tetrahydronaphthalenyl, A isphenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is dihydrobenzodioxepinyl, A isphenyl, and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is acyclic, where the various moieties are independentlyselected, Ar¹ is pyridinyl, R¹ is H, R² is alkoxyalkyl, A is phenyl, andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR¹R² is piperidinyl, and z, X, L, A, Q, and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar^(t) is aryl, NR R² is morpholinyl, and z, X, L, A, Q, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR¹R² is piperazinyl, and z, X, L, A, Q, and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azapenyl, and z, X, L, A, Q, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azetidinyl, and z, X, L, A, Q, and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is oxaazabicyclooctanyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azabicycloheptanyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is dihydrobenzoxazinyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is dihydroindolyl, and z, X, L, A, Q, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is thiomorpholinyl, and z, X, L, A, Q, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar is aryl, NR R² is azatricyclotridecapentaenyl, and z, X, L,A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azaspirodecanyl, and z, X, L, A, Q, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar^(t) is aryl, NR R² is azaspiroundecanyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is tetrahydronaphthyridinyl, and z, X, L,A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azabicyclooctanyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is diazepanyl, and z, X, L, A, Q, and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is decahydroquinolinyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is diazaspiroundecanyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is tetrahydroisoquinolinyl, and z, X, L, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is piperidinyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is morpholinyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar is heteroaryl, NR¹R² is piperazinyl, and z, X, L, A, Q, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azapenyl, and z, X, L, A, Q, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar^(t) is heteroaryl, NR¹R² is azetidinyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is oxaazabicyclooctanyl, and z, X, L,A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azabicycloheptanyl, and z, X, L,A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is dihydrobenzoxazinyl, and z, X, L,A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is dihydroindolyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is thiomorpholinyl, and z, X, L, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azatricyclotridecapentaenyl, andz, X, L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azaspirodecanyl, and z, X, L, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azaspiroundecanyl, and z, X, L, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is tetrahydronaphthyridinyl, and z,X, L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azabicyclooctanyl, and z, X, L, A,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar^(t) is heteroaryl, NR¹R² is diazepanyl, and z, X, L, A, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is decahydroquinolinyl, and z, X, L,A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is diazaspiroundecanyl, and z, X, L,A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is tetrahydroisoquinolinyl, and z, X,L, A, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR¹R² is piperidinyl, A is phenyl, and z, X, L,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is morpholinyl, A is phenyl and z, X, L, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR¹R² is piperazinyl, A is phenyl and z, X, L, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azapenyl, A is phenyl and z, X, L, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azetidinyl, A is phenyl and z, X, L, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar is aryl, NR R² is oxaazabicyclooctanyl, A is phenyl and z,X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azabicycloheptanyl, A is phenyl and z,X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar^(t) is aryl, NR R² is dihydrobenzoxazinyl, A is phenyl andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR¹R² is dihydroindolyl, A is phenyl and z, X, L,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is thiomorpholinyl, A is phenyl and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azatricyclotridecapentaenyl, A is phenyland z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is azaspirodecanyl, A is phenyl and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar is aryl, NR R² is azaspiroundecanyl, A is phenyl and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic), where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is tetrahydronaphthyridinyl, A is phenyland z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar is aryl, NR R² is azabicyclooctanyl, A is phenyl and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is diazepanyl, A is phenyl and z, X, L, Q,and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar^(t) is aryl, NR R² is decahydroquinolinyl, A is phenyl andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR¹R² is diazaspiroundecanyl, A is phenyl and z,X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is aryl, NR R² is tetrahydroisoquinolinyl, A is phenyl andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is piperidinyl, A is phenyl and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is morpholinyl, A is phenyl and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is piperazinyl, A is phenyl and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azapenyl, A is phenyl and z, X, L,Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azetidinyl, A is phenyl and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is oxaazabicyclooctanyl, A is phenyland z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azabicycloheptanyl, A is phenyland z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is dihydrobenzoxazinyl, A is phenyland z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar^(t) is heteroaryl, NR¹R² is dihydroindolyl, A is phenyl andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is thiomorpholinyl, A is phenyl andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azatricyclotridecapentaenyl, A isphenyl and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azaspirodecanyl, A is phenyl andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azaspiroundecanyl, A is phenyl andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is tetrahydronaphthyridinyl, A isphenyl and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is azabicyclooctanyl, A is phenyl andz, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is diazepanyl, A is phenyl and z, X,L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar^(t) is heteroaryl, NR¹R² is decahydroquinolinyl, A isphenyl and z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is diazaspiroundecanyl, A is phenyland z, X, L, Q, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where NR R² is cyclic, where the various moieties are independentlyselected, Ar¹ is heteroaryl, NR¹R² is tetrahydroisoquinolinyl, A isphenyl and z, X, L, Q, and R³ are as defined.

Another embodiment of this invention is the provision of compounds,compositions, kits, and antidotes for the NAMPT pathway in mammalshaving a compound of the Formula II:

Ar¹-(CHR)_(n)-L-Ar²—X—R¹  II

wherein

-   Ar¹ is aryl, heteroaryl or heterocycloalkyl, wherein the heteroatom    of each of said heteroaryl and heterocycloalkyl numbers 1, 2 or 3,    and is independently selected from N, S or O, further wherein each    of said aryl, heteroaryl and heterocycloalkyl may independently be    either substituted or fused with aryl, heteroaryl or    heterocycloalkyl, still further wherein any of said aryl, heteroaryl    and heterocycloalkyl is either unsubstituted or optionally    independently substituted with one or more substituents which can be    the same or different and are independently selected from the group    consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z),    alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-,    (alkoxyalkyl)amino-, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl,    —N(R³)—C(O)—O-alkyl, —N(R³)—C(O)—O-aryl, -cycloalkyl,    -heterocycloalkyl, -aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl,    with the proviso that no two adjacent ring heteroatoms are both S or    both O;-   R is H, a straight or branched C₁-C₆ alkyl, or arylalkyl;-   n is 0, 1, 2, 3 or 4;-   L is selected from NHC(O)NH, OC(O)NH, NHC(O)O, OCH₂C(O)NH, C(O)NH,    NHC(S)NH, OC(S)NH, NHC(S)O, OCH₂C(S)NH, or C(S)NH, with the proviso    that when L is C(O)NH, then n is 0;-   Ar² is aryl, heteroaryl, heterocycloalkyl or C₃ to C₈ cycloalkyl,    with each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl    being either unsubstituted or optionally independently substituted    with 1, 2, 3 or 4 substituents which can be the same or different    and are independently selected from the group consisting of    deuterium, halo, cyano, isocyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z), —OCH_(z)F_(3-z),    alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-,    (alkoxyalkyl)amino-, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl,    —N(R³)—C(O)—O-alkyl, —N(R³)—C(O)—O-aryl, -cycloalkyl,    -heterocycloalkyl,-aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl;-   X is S, S(O), S(O)₂, O or C(O);-   R¹ is cycloalkyl, —CH_(z)F_(3-z), aryl, heterocycloalkyl,    heteroaryl, alkyl, -alkenyl, -alkynyl, (aryl)alkyl-,    (heteroaryl)alkyl- or (heterocycloalkyl)alkyl-, (i) wherein each of    said cycloalkyl, aryl, heterocycloalkyl, heteroaryl and alkyl is    either unsubstituted or optionally substituted with 1, 2, 3, 4 or 5    substituents which can be the same or different and are    independently selected from the group consisting of deuterium, halo,    cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),    —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3-z),    —OCH_(z)F_(3-z), alkyl, -alkenyl, -alkynyl, alkoxy-, hydroxy,    -alkylhydroxy, aryloxy- or (alkoxyalkyl)amino-, -cycloalkyl,    -heterocycloalkyl,-aryl, —S(O)₂-alkyl, —S(O)₂-aryl, —S(O)₂—CF₃,    —C(O)N(alkyl)₂, —C(O)alkyl, —NH—C(O)-alkyl, —NH—C(O)-aryl,    methylenedioxy, and heteroaryl, (ii) further wherein each of said    cycloalkyl, aryl, heterocycloalkyl, and heteroaryl may additionally    optionally be fused with independently selected aryl, heteroaryl,    heterocycloalkyl or cyloalkyl;-   R³ is H, alkyl or arylalkyl-;-   z is 0, 1, or 2;    and pharmaceutically acceptable salts, solvates, esters, prodrugs    and isomers thereof, with the proviso that the compound of Formula I    is not    3-{1-[(4-methoxybenzene)sulfonyl]piperidin-4-yl}-1-(pyridin-3-ylmethyl)urea,    or 1-(4-phenoxyphenyl)-3-(pyridin-3-ylmethyl)thiourea.

In the compounds of Formula II, the various moieties are independentlyselected.

The following embodiments are directed to Formula II as applicable.Further, the moieties aryl, heteroaryl, heterocycloalkyl, cycloalkyl,spiroheterocycloalkyl and heterospiroheterocycloalkyl as well as theirrepresentative moieties in these embodiments can be independentlyunsubstituted or optionally substituted or optionally fused as describedearlier. Any one or more of the embodiments relating to Formula II belowcan be combined with one or more other embodiments of Formula II.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,and z, X, L, n, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, and z, X, L, n, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheterocycloalkyl, and z, X, L, n, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is arylfused with an aryl, heteroaryl or heterocycloalkyl, and z, X, L, n, Ar²,R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl fused with an aryl, heteroaryl or heterocycloalkyl, and z, X,L, n, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheterocycloalkyl fused with an aryl, heteroaryl or heterocycloalkyl, andz, X, L, n, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is arylsubstituted as shown under Formula II, and z, X, L, n, Ar², R¹ and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl substituted as shown under Formula II, and z, X, L, n, Ar²,R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheterocycloalkyl substituted as shown under Formula II, and z, X, L, n,Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is H, and z, X, L, n, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a straight chain alkyl, and z, X, L, n, Ar², R¹ and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a branched chain alkyl, and z, X, L, n, Ar², R¹ and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is H, n is 1, and z, X, L, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a straight chain alkyl, n is 1, and z, X, L, Ar², R¹ and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a branched chain alkyl, n is 1, and z, X, L, Ar², R¹ and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is H, n is 1, L is —N(H)—C(O)—N(H)—, and z, X, Ar², R¹ and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, and z, X,Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, and z, X,Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O₂)—, and z, Ar², R¹ andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is—S(O₂)—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is—S(O₂)—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, and z, Ar², R¹ andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—,and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—,and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, and z, Ar², R¹ andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—,and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—,and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, and z, Ar², R¹ and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—,and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ is aryl,R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—,and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, and z, X, L, n, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, and z, X, L, n, Ar², R¹ and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, and z, X, L, n, Ar², R¹ and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, and z, X, L, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, and z, X, L, Ar², R¹and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, and z, X, L, Ar², R¹and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O₂)—, and z,Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, and z,Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, and z,Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, and z, Ar²,R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, and z, Ar², R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, Ar² is aryl, and z, X, L, n, R¹ and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, and z, X, L, n, R¹and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, and z, X, L, n, R¹and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, Ar² is aryl, and z, X, L, R¹ and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, n is 1, and z, X,L, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, n is 1, and z, X,L, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O₂)—, Ar² isaryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar² isaryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar² isaryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, Ar² is aryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, Ar² is aryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar² isaryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, and z, R¹ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, Ar² is aryl, R¹ is cycloalkyl, and z, X, L, n, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, R¹ is cycloalkyl,and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound, ofFormula II where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, R¹ is cycloalkyl,and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, Ar² is aryl, R¹ is cycloalkyl, and z, X, L,n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, n is 1, R¹ iscycloalkyl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, n is 1, R¹ iscycloalkyl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O₂)—, Ar² isaryl, R¹ is cycloalkyl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, R¹ is cycloalkyl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, R¹ is cycloalkyl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar² isaryl, R¹ is cycloalkyl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, R¹ is cycloalkyl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, R¹ is cycloalkyl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar² isaryl, R¹ is cycloalkyl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, Ar² is aryl, R¹ is cycloalkyl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, Ar² is aryl, R¹ is cycloalkyl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar² isaryl, R¹ is cycloalkyl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, R¹ is cycloalkyl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, R¹ is cycloalkyl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, Ar² is aryl, R¹ is aryl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, R¹ is aryl, and z,X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, R¹ is aryl, and z,X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, Ar² is aryl, R¹ is aryl, and z, X, L, n, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, n is 1, R¹ isaryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, n is 1, R¹ isaryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O₂)—, Ar² isaryl, R¹ is aryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, R¹ is aryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, R¹ is aryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar² isaryl, R¹ is aryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, R¹ is aryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, R¹ is aryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar² isaryl, R¹ is aryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, Ar² is aryl, R¹ is aryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, Ar² is aryl, R¹ is aryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar² isaryl, R¹ is aryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, R¹ is aryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, R¹ is aryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, Ar² is heteroaryl, R¹ is aryl, and z, X, L, n, andR³ are as defined.

An embodiment of the invention is the provision of a compound, ofFormula II where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, R¹ is heteroaryl,and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, R¹ is heteroaryl,and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, Ar² is aryl, R¹ is heteroaryl, and z, X, L,n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, n is 1, R¹ isheteroaryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, n is 1, R¹ isheteroaryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O₂)—, Ar² isaryl, R¹ is heteroaryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, R¹ is heteroaryl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, R¹ is heteroaryl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar² isaryl, R¹ is heteroaryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, R¹ is heteroaryl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, R¹ is heteroaryl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar² isaryl, R¹ is heteroaryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, Ar² is aryl, R¹ is heteroaryl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, Ar² is aryl, R¹ is heteroaryl, and z, X, L, n, and R³ areas defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar² isaryl, R¹ is heteroaryl, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, R¹ is heteroaryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, R¹ is heteroaryl, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, Ar² is heteroaryl, R¹ is CF₃, and z, X, L, n, and R³are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, R¹ is CF₃, and z,X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, R¹ is CF₃, and z,X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, Ar² is aryl, R¹ is CF₃, and z, X, L, n, andR³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, Ar² is aryl, n is 1, R¹ is CF₃,and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, Ar² is aryl, n is 1, R¹ is CF₃,and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O₂)—, Ar² isaryl, R¹ is CF₃, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, R¹ is CF₃, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O₂)—, Ar² is aryl, R¹ is CF₃, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar² isaryl, R¹ is CF₃, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, R¹ is CF₃, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —S(O)—, Ar² is aryl, R¹ is CF₃, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar² isaryl, R¹ is CF₃, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound, where thevarious moieties are independently selected, Ar¹ is heteroaryl, R is astraight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar² isaryl, R¹ is CF₃, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —C(O)—, Ar² is aryl, R¹ is CF₃, and z, X, L, n, and R³ are asdefined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar² isaryl, R¹ is CF₃, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, R¹ is CF₃, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isheteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—,X is —O—, Ar² is aryl, R¹ is CF₃, and z, X, L, n, and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, Ar¹ isselected from the group consisting of pyridinyl, imidazopyridinyl,pyrazolyl, quinolinyl and thienopyridinyl.

Each of these moieties may be unsubstituted or optionally independentlysubstituted with one or more groups which can be the same or differentand are independently selected from the group consisting of —NH₂,—N(alkyl)₂, (alkoxyalkyl)oxy-, and pyrazolyl.

An embodiment of the invention is the provision of a compound of FormulaII, where the various moieties are independently selected, R¹ isselected from the group consisting of cyclopentyl, CF₃, phenyl,naphthalenyl, pyrimidinyl, oxazolyl, 8-oxatricyclotridecahexaenyl andthienyl. Each of these moieties may be unsubstituted or optionallyindependently substituted with one or more groups which can be the sameor different and are independently selected from the group consisting of—C(O)NH₂, —S(O₂)CH₃, F, Cl, Br, methylenedioxy, CF₃, OCF₃, alkyl,alkoxy, pyrazolyl, C(O)CH₃ and phenoxy.

An especially preferred moiety for Ar¹-(CHR)_(n)-L—in Formula II is themoiety:

Another aspect of this invention is the provision of compounds,compositions, kits, and antidotes for the NAMPT pathway in mammalsderived from compounds of Formula I and Formula II and having theFormula III:

wherein,

Ar¹ is 5 to 12 membered heteroaryl comprising 1, 2, 3 or 4 heteroatom(s)independently selected from N, S or O, wherein said heteroaryl isunsubstituted or substituted by one or more R^(a) selected from thegroup consisting of —NH₂, oxo, halo, haloalkyl, —NH(CO)O-alkyl, —C(O)NH₂and 3,4-dihydroxy-5-methyltetrahydrofurane; and wherein said heteroarylcan comprise one or more N-oxide(s) formed with a N atom member of saidheteroaryl, with the proviso that no two adjacent ring heteroatoms areboth S or both O;

Ar² is aryl or 5 or 6 membered heteroaryl comprising 1, 2, 3 or 4heteroatom(s) independently selected from N, S or O;

R is H, a straight or branched C₁-C₆ alkyl, or arylalkyl;

R¹ is —NR³R⁴ wherein R³ is H, alkyl or —S(O)₂alkyl and R⁴ is alkyl,hydroxyalkyl, —S(O)₂alkyl, —(CH₂)_(q)cycloalkyl,—(CH₂)_(q)heterocycloalkyl, aryl, arylalkyl-, —(CH₂)_(q)heteroaryl;haloalkyl, cycloalkyl; aryl; heterocycloalkyl; or heteroaryl; wherein:

-   -   each of said cycloalkyl, aryl, or heteroaryl is unsubstituted or        substituted with 1, 2, 3, 4 or 5 substituents which can be the        same or different and are independently selected from the group        consisting of:        -   deuterium, halo, cyano, alkyl, hydroxyl, hydroxyalkyl,            hydroxyalkoxy, cyanoalkyl, haloalkyl, alkenyl, alkynyl,            alkoxy, alkylalkoxy, haloalkoxy, arylalkenyl-, aryloxy,            benzyloxy, oxo, —(CH₂)_(q)—NR^(b)R^(c),            —(CH₂)_(q)—CONR^(b)R^(c), —S(O)₂-alkyl, —S(O)₂-aryl,            —S(O)₂NH-alkyl, —S(O)₂N(alkyl)₂, —S(O)₂-heterocycloalkyl,            —S(O)₂—CF₃, —C(O)alkyl, —C(O)aryl, —C(O)alkylenylaryl,            —C(O)O-alkyl, —NH—C(O)alkyl, —NH—C(O)aryl, methylenedioxy,            —(CH₂)_(q)cycloalkyl, cycloalkylalkoxy-, aryl, arylalkyl-,            —(CH₂)_(q)heteroaryl, and —(CH₂)_(q)heterocycloalkyl,            wherein each of said cycloalkyl, heterocycloalkyl, aryl or            heteroaryl may be substituted by one or more halo, nitro,            haloalkyl, haloalkoxy, oxo, cyano, alkyl, haloalkyl, or            alkoxy and;    -   each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl        may optionally additionally be fused with independently selected        aryl, heteroaryl, heterocycloalkyl or cycloalkyl to from a        bicyclic or tricyclic group that may be substituted by one or        more halo, cyano, alkyl or alkoxy;

R² is O or absent,

R^(b) and R^(c) are independently selected from the group consisting ofH, alkyl, hydroxyalkyl, alkoxy, aryl, alkoxyalkyl, —S(O)₂alkyl andcycloalkyl or R^(b) and R^(c) can form a 5 or 6 memberedheterocycloalkyl group together with the nitrogen atom to which they areattached, wherein said heterocycloalkyl group may contain one or moreadditional heteroatom(s) selected from N, S or O;

n is 0, or 1;

q is 0, 1 or 2;

and pharmaceutically acceptable salts, solvates, esters and isomersthereof,

with the proviso that the compound of Formula I is not1-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea,3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea or3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

In an embodiment, this invention discloses compounds of Formula III andpharmaceutically acceptable salts, solvates, ester or isomers thereof.

In the compounds of Formula III, the various moieties are independentlyselected.

The following embodiments are directed to Formula III as applicable.Further, the moieties aryl, heteroaryl, heterocycloalkyl, cycloalkyl,spiroheterocycloalkyl and heterospiroheterocycloalkyl as well as theirrepresentative moieties in these embodiments can be independentlyunsubstituted or optionally substituted or optionally fused as describedearlier. Any one or more of the embodiments related to Formula III belowcan be combined with one or more other embodiments of Formula III.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and Ar² isaryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and Ar² isphenyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and Ar² hasthe following formula:

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and Ar¹ ispyridine.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and Ar¹ hasthe following formula:

where R^(a) is selected from the group consisting of —NH₂, oxo, halo,haloalkyl, —NH(CO)O-alkyl, —C(O)NH₂ and3,4-dihydroxy-5-methyltetrahydrofurane.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and Ar¹ hasthe formula of:

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and n is 1.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and n is 1.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1 and Ar² is aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1 and Ar² is phenyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and Ar² is phenyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and Ar² hasthe following formula:

and Ar¹ is pyridine.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R is H.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R is H.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, n is 1 and Ris H.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R is H.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, n is 1, Ar²is phenyl and R is H.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R is H.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ is—NR³R⁴ wherein R³ is H, alkyl or —S(O)₂alkyl and R⁴ is alkyl,hydroxyalkyl, —S(O)₂alkyl, —(CH₂)_(q)cycloalkyl,—(CH₂)_(q)heterocycloalkyl, aryl, arylalkyl-, —(CH₂)_(q)heteroaryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ is—NR³R⁴ wherein R³ is H and R⁴ is aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is —NR³R⁴ wherein R³ is H and R⁴ is aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is —NR³R⁴ wherein R³ is H and R⁴ is aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is —NR³R⁴ wherein R³ is H and R⁴ is aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is —NR³R⁴ wherein R³ is H and R⁴ is aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is —NR³R⁴ wherein R³ is H and R⁴is aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ ishaloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is haloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is haloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is haloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is haloalkyl.

An embodiment of the invention is the provision of a compound, where thevarious moieties are independently selected, Ar¹ is pyridine, Ar² isphenyl and R¹ is haloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is haloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is haloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted C₃-C₁₂-cycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted C₃-C₂-cycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is unsubstituted or substituted C₃-C₁₂-cycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substitutedC₃-C₁₂-cycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is unsubstituted or substitutedC₃-C₁₂-cycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is unsubstituted or substitutedC₃-C₁₂-cycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted C₃-C₁₂-cycloalkyl, wherein the cycloalkylis selected from the group consisting of cyclopropyl, cyclopentane,cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan,bicyclo[3.1.1]heptan, adamantane, and(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted C₃-C₁₂-cycloalkyl,wherein the cycloalkyl is selected from the group consisting ofcyclopropyl, cyclopentane, cycloheptyl, azaspiro[4.5]decane,bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan, adamantane, and(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is unsubstituted or substituted C₃-C₁₂-cycloalkyl, whereinthe cycloalkyl is selected from the group consisting of cyclopropyl,cyclopentane, cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan,bicyclo[3.1.1]heptan, adamantane, and(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substitutedC₃-C₁₂-cycloalkyl, wherein the cycloalkyl is selected from the groupconsisting of cyclopropyl, cyclopentane, cycloheptyl,azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan,adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is unsubstituted or substitutedC₃-C₁₂-cycloalkyl, wherein the cycloalkyl is selected from the groupconsisting of cyclopropyl, cyclopentane, cycloheptyl,azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan,adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is unsubstituted or substitutedC₃-C₁₂-cycloalkyl, wherein the cycloalkyl is selected from the groupconsisting of cyclopropyl, cyclopentane, cycloheptyl,azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan,adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted C₆-C₁₀-aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted C₆-C₁₀-aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is unsubstituted or substituted C₆-C₁₀-aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substitutedC₆-C₁₀-aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is unsubstituted or substituted C₆-C₁₀-aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is unsubstituted or substitutedC₆-C₁₀-aryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted C₆-C₁₀-aryl, wherein the aryl is selectedfrom the group consisting of phenyl, naphatalene, tetrahydronaphthalene,and 1H-inden-5-yl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted C₆-C₁₀-aryl, wherein thearyl is selected from the group consisting of phenyl, naphatalene,tetrahydronaphthalene, and 1H-inden-5-yl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is unsubstituted or substituted C₆-C₁₀-aryl, wherein thearyl is selected from the group consisting of phenyl, naphatalene,tetrahydronaphthalene, and 1H-inden-5-yl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substitutedC₆-C₁₀-aryl, wherein the aryl is selected from the group consisting ofphenyl, naphatalene, tetrahydronaphthalene, and 1H-inden-5-yl.

An embodiment of the invention is the provision of a compound, where thevarious moieties are independently selected, Ar¹ is pyridine, n is 1,and R¹ is unsubstituted or substituted C₆-C₁₀-aryl, wherein the aryl isselected from the group consisting of phenyl, naphatalene,tetrahydronaphthalene, and 1H-inden-5-yl. An embodiment of the inventionis the provision of a compound of Formula III, where the variousmoieties are independently selected, Ar¹ is pyridine, n is 1, Ar² isphenyl and R¹ is unsubstituted or substituted C₆-C₁₀-aryl, wherein thearyl is selected from the group consisting of phenyl, naphatalene,tetrahydronaphthalene, and 1H-inden-5-yl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted heterocycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted heterocycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is unsubstituted or substituted heterocycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substitutedheterocycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² is aryland R¹ is unsubstituted or substituted heterocycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is unsubstituted or substitutedheterocycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is unsubstituted or substitutedheterocycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted 5 to 12 membered heterocycloalkylcomprising 1, 2 or 3 heteroatoms selected from N, O and S.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted 5 to 12 memberedheterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O andS.

An embodiment of the invention is the provision of a compound, where thevarious moieties are independently selected, Ar² is phenyl and R¹ isunsubstituted or substituted 5 to 12 membered heterocycloalkylcomprising 1, 2 or 3 heteroatoms selected from N, O and S.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substituted 5 to 12membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected fromN, O and S.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is unsubstituted or substituted 5 to 12membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected fromN, O and S.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is unsubstituted or substituted 5to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatomsselected from N, O and S.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted 5 to 12 membered heterocycloalkylcomprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein theheterocycloalkyl is selected from the group consisting of azetidine,piperidine, pyrrolidine, piperazine, thiophorpholine,2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane,1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted 5 to 12 memberedheterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O andS, wherein the heterocycloalkyl is selected from the group consisting ofazetidine, piperidine, pyrrolidine, piperazine, thiophorpholine,2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane,1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is unsubstituted or substituted 5 to 12 memberedheterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O andS, wherein the heterocycloalkyl is selected from the group consisting ofazetidine, piperidine, pyrrolidine, piperazine, thiophorpholine,2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane,1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substituted 5 to 12membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected fromN, O and S, wherein the heterocycloalkyl is selected from the groupconsisting of azetidine, piperidine, pyrrolidine, piperazine,thiophorpholine, 2,8-diazaspiro[5.5]undecane,8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane,2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is unsubstituted or substituted 5 to 12membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected fromN, O and S, wherein the heterocycloalkyl is selected from the groupconsisting of azetidine, piperidine, pyrrolidine, piperazine,thiophorpholine, 2,8-diazaspiro[5.5]undecane,8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane,2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is unsubstituted or substituted 5to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatomsselected from N, O and S, wherein the heterocycloalkyl is selected fromthe group consisting of azetidine, piperidine, pyrrolidine, piperazine,thiophorpholine, 2,8-diazaspiro[5.5]undecane,8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane,2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted heteroaryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted heteroaryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is unsubstituted or substituted heteroaryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substitutedheteroaryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² is aryland R¹ is unsubstituted or substituted heteroaryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is unsubstituted or substituted heteroaryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is unsubstituted or substitutedheteroaryl.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3heteroatoms selected from N, O and S.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted 5 to 12 heteroarylcomprising 1, 2 or 3 heteroatoms selected from N, O and S.

An embodiment of the invention is the provision of a compound, where thevarious moieties are independently selected, Ar² is phenyl and R¹ isunsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3heteroatoms selected from N, O and S.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substituted 5 to 12heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is unsubstituted or substituted 5 to 12heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is unsubstituted or substituted 5to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O andS.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected and R¹ isunsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3heteroatoms selected from N, O and S, wherein the heteroaryl is selectedfrom the group consisting of 1,3,4-oxadiazol,(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine,3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol,3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline,indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole,8-oxatricyclo[7.4.0.0²,⁷]trideca-1(9),2(7),3,5,10,12-hexaene,5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine,3-azaspiro[5.5]undecane,azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene,(4aR,8aS)-decahydroisoquinoline, and5,6,7,8-tetrahydro-1,6-naphthyridine.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine and R¹ is unsubstituted or substituted 5 to 12 heteroarylcomprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein theheteroaryl is selected from the group consisting of 1,3,4-oxadiazol,(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine,3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol,3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline,indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole,8-oxatricyclo[7.4.0.0²,7]trideca-1(9),2(7),3,5,10,12-hexaene,5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine,3-azaspiro[5.5]undecane,azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene,(4aR,8aS)-decahydroisoquinoline, and5,6,7,8-tetrahydro-1,6-naphthyridine.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar² isphenyl and R¹ is unsubstituted or substituted 5 to 12 heteroarylcomprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein theheteroaryl is selected from the group consisting of 1,3,4-oxadiazol,(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine,3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol,3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline,indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole,8-oxatricyclo[7.4.0.0²,⁷]trideca-1(9),2(7),3,5,10,12-hexaene,5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine,3-azaspiro[5.5]undecane,azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene,(4aR,8aS)-decahydroisoquinoline, and5,6,7,8-tetrahydro-1,6-naphthyridine.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, Ar² is phenyl and R¹ is unsubstituted or substituted 5 to 12heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S,wherein the heteroaryl is selected from the group consisting of1,3,4-oxadiazol, (1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine,3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol,3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline,indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole,8-oxatricyclo[7.4.0.0²,⁷]trideca-1(9),2(7),3,5,10,12-hexaene,5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine,3-azaspiro[5.5]undecane,azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene,(4aR,8aS)-decahydroisoquinoline, and5,6,7,8-tetrahydro-1,6-naphthyridine.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, and R¹ is unsubstituted or substituted unsubstitutedor substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatomsselected from N, O and S, wherein the heteroaryl is selected from thegroup consisting of 1,3,4-oxadiazol,(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine,3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol,3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline,indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole,8-oxatricyclo[7.4.0.0²,⁷]trideca-1(9),2(7),3,5,10,12-hexaene,5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine,3-azaspiro[5.5]undecane,azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene,(4aR,8aS)-decahydroisoquinoline, and5,6,7,8-tetrahydro-1,6-naphthyridine.

An embodiment of the invention is the provision of a compound of FormulaIII, where the various moieties are independently selected, Ar¹ ispyridine, n is 1, Ar² is phenyl and R¹ is unsubstituted or substitutedunsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3heteroatoms selected from N, O and S, wherein the heteroaryl is selectedfrom the group consisting of 1,3,4-oxadiazol,(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine,3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol,3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline,indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole,8-oxatricyclo[7.4.0.0²,⁷]trideca-1(9),2(7),3,5,10,12-hexaene,5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine,3-azaspiro[5.5]undecane,azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene,(4aR,8aS)-decahydroisoquinoline, and5,6,7,8-tetrahydro-1,6-naphthyridine.

Another embodiment of the invention is the provision of a compound ofFormula III where Ar¹ is pyridine, n is 1, Ar² is phenyl and the Formulabecomes Formula III A:

wherein R¹ and R^(a) are as defined in Formula III with the proviso thatthe compounds are notN-[4-(phenylsulfonyl)phenyl]-N′-(3-pyridinylmethyl)urea,N,N-diethyl-4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide,or 4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide.

Another embodiment of the invention is compounds of Formula III whereAr² is phenyl and Ar1 has the structure of

and the formula becomes Formula IIIB

wherein:

-   R^(a) is one of more and can be selected from the group consisting    of amino, oxo, halo, halo(C₁-C₆)alkyl, —NH(CO)O—(C₁-C₆)alkyl and    —C(O)NH₂; and wherein said pyridine can comprise a N-oxide formed    with its N atom member;-   R¹ is —NR³R⁴ wherein R³ is H, C₁-C₆-alkyl or —S(O)₂(C₁-C₆)alkyl and    R⁴ is (C₁-C₆)alkyl, hydroxy(C₁-C₆)alkyl, —S(O)₂(C₁-C₆)alkyl,    —(CH₂)_(q)cycloalkyl, —(CH₂)_(q)heterocycloalkyl, aryl,    aryl(C₁-C₆)alkyl-, —(CH₂)_(q)heteroaryl;    -   halo(C₁-C₆)alkyl,    -   cycloalkyl;    -   aryl;    -   heterocycloalkyl; or    -   heteroaryl    -   wherein:        -   each of said cycloalkyl, aryl, or heteroaryl is            unsubstituted or substituted with 1, 2, 3, 4 or 5            substituents which can be the same or different and are            independently selected from the group consisting of:            -   halo, cyano, (C₁-C₆)alkyl, hydroxyl,                hydroxy(C₁-C₆)alkyl, hydroxy(C₁-C₆)alkoxy,                halo(C₁-C₆)alkyl, (C₁-C₆)alkoxy,                (C₁-C₆)alkyl(C₁-C₆)alkoxy, halo(C₁-C₆)alkoxy,                aryl(C₂-C₆)alkenyl-, aryloxy, benzyloxy, oxo,                —(CH₂)_(q)—NR^(b)R^(c), —(CH₂)_(q)—CONR^(b)R^(c),                —S(O)₂—(C₁-C₆)alkyl, —S(O)₂NH—(C₁-C₆)alkyl,                —S(O)₂-heterocycloalkyl, —S(O)₂—CF₃, —C(O)(C₁-C₆)alkyl,                —C(O)aryl, —C(O) (C₂-C₆)alkylenylaryl,                —C(O)O—(C₁-C₆)alkyl, —(CH₂)_(q)cycloalkyl,                cycloalkyl(C₁-C₆)alkoxy-, aryl, aryl(C₁-C₆)alkyl-,                —(CH₂)_(q)heteroaryl, and —(CH₂)_(q)heterocycloalkyl,                wherein each of said cycloalkyl, heterocycloalkyl, aryl                or heteroaryl may be substituted by one or more halo,                nitro, halo(C₁-C₆)alkyl, halo(C₁-C₆)alkoxy, oxo, cyano,                (C₁-C₆)alkyl, halo(C₁-C₆)alkyl, or (C₁-C₆)alkoxy;-   R^(b) and R^(c) are independently selected from the group consisting    of H, (C₁-C₆)alkyl, hydroxy(C₁-C₆)alkyl, (C₁-C₆)alkoxy, aryl,    (C₁-C₆)alkoxy(C₁-C₆)alkyl, —S(O)₂(C₁-C₆)alkyl and (C₃-C₆)cycloalkyl    or R^(b) and R^(c) can form a 5 or 6 membered heterocycloalkyl group    together with the nitrogen atom to which they are attached, wherein    said heterocycloalkyl group may contain one or more additional    heteroatom(s) selected from N, S or O    q is 0 or 1; and    pharmaceutically acceptable salts thereof,    with the proviso that the compounds of Formula Ia are not:    N-[4-(phenylsulfonyl)phenyl]-N′-(3-pyridinylmethyl)urea,    N,N-diethyl-4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide,    or 4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide.

An embodiment of the invention is compounds of Formula IIIB, wherein R¹is —NR³R⁴ wherein R³ is H, alkyl or —S(O)₂alkyl and R⁴ is alkyl,hydroxyalkyl, —S(O)₂alkyl, —(CH₂)_(q)cycloalkyl,—(CH₂)_(q)heterocycloalkyl, aryl, arylalkyl-, —(CH₂)_(q)heteroaryl.

Another embodiment of the invention is compounds of Formula IIIB, whereR is NR³R⁴ wherein R³ is H and R⁴ is aryl.

Another embodiment of the invention is compounds of Formula IIIB whereinR¹ is haloalkyl.

Another embodiment of the invention is compounds of Formula IIIB whereinR¹ is unsubstituted or substituted C₃-C₁₂-cycloalkyl.

Still another embodiment of the invention is compounds of Formula IIIB,wherein R¹ is unsubstituted or substituted C₃-C₁₂-cycloalkyl and thecycloalkyl is selected from the group consisting of cyclopropyl,cyclopentane, cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan,bicyclo[3.1.1]heptan, adamantane, and(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

Yet another embodiment of the invention is compounds of Formula IIIBwherein R¹ is unsubstituted or substituted C₆-C₁₀-aryl.

A further embodiment of the invention is compounds of Formula III Bwherein R is unsubstituted or substituted C₆-C₁₀-aryl and the aryl isselected from the group consisting of phenyl, naphatalene,tetrahydronaphthalene, and 1H-inden-5-yl.

Another embodiment of the invention is compounds of Formula IIIB,wherein R¹ is unsubstituted or substituted heterocycloalkyl.

One embodiment of the invention is compounds of Formula III B, whereinR¹ is unsubstituted or substituted 5 to 12 membered heterocycloalkylcomprising 1, 2 or 3 heteroatoms selected from N, O and S.

One embodiment of the invention is compounds of Formula IIIB, wherein R¹is unsubstituted or substituted 5 to 12 membered heterocycloalkylcomprising 1, 2 or 3 heteroatoms selected from N, O and S, and theheterocycloalkyl is selected from the group consisting of azetidine,piperidine, pyrrolidine, piperazine, thiophorpholine,2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane,1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

Another embodiment of the invention is compounds of Formula IIIB,wherein R¹ is unsubstituted or substituted heteroaryl.

Another embodiment of the invention is compounds of Formula IIIB,wherein R¹ is unsubstituted or substituted 5 to 12 heteroaryl comprising1, 2 or 3 heteroatoms selected from N, O and S.

Still another embodiment of the invention is compounds of Formula IIIB,wherein R¹ is unsubstituted or substituted 5 to 12 heteroaryl comprising1, 2 or 3 heteroatoms selected from N, O and S, and the heteroaryl isselected from the group consisting of 1,3,4-oxadiazol,(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine,3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol,3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline,indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole,8-oxatricyclo[7.4.0.0²,⁷]trideca-1(9),2(7),3,5,10,12-hexaene,5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine,3-azaspiro[5.5]undecane,azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene,(4aR,8aS)-decahydroisoquinoline, and5,6,7,8-tetrahydro-1,6-naphthyridine Illustrative compounds of theinvention are:

Structure Chemical Name

1-(pyridin-3-ylmethyl)-3-(4-{[2- (trifluoromethoxy)benzene]sulfonyl}phenyl)urea

3-{4-[(4-bromobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-(4-{[2-methyl-4-(1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

N-[2-(pyridin-3-yl)ethyl]-4-{[3- (trifluoromethoxy)benzene]sulfonyl}benzamide

3-{4-[(4-methoxy-2- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2,4- dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-[(6-aminopyridin-3-yl)methyl]-3-{4-[(4-fluorobenzene)sulfonyl]phenyl}urea

3-{4-[(3,5- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-[(6-aminopyridin-3-yl)methyl]-3-[4- (benzenesulfonyl)phenyl]urea

3-{4-[(4-methylbenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-pyrazol-1-yl)pyridin-3-yl]methyl}urea

3-(4-{[2-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea

4-(benzenesulfonyl)-N-{imidazo[1,2- a]pyridin-7-ylmethyl}benzamide

3-{4-[(2-bromobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

4-(benzenesulfonyl)-N-(pyridin-3- ylmethyl)benzamide

3-{4-[(2-ethoxybenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-imidazol-1-yl)pyridin-3-yl]methyl}urea

3-{4-[(3,4- dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{[({4-[(4- chlorobenzene)sulfinyl]phenyl}carbamoyl)amino]methyl}pyridin-1-ium-1-olate

1-(pyridin-3-ylmethyl)-3-(4-{[4-(trifluoromethyl)benzene]sulfonyl}phenyl) urea

3-{4-[(2,5- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[3- (trifluoromethoxy)benzene]sulfonyl}phenyl)urea

N,N-dimethyl-4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide

3-(4-{[2-methoxy-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin- 3-ylmethyl)urea

3-[4-(benzenesulfonyl)phenyl]-1-(pyridin- 3-ylmethyl)urea

1-[4-(benzenesulfonyl)phenyl]-3-(1H- pyrazol-3-ylmethyl)urea

3-{4-[(3-bromobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[3- (trifluoromethyl)benzene]sulfonyl}phenyl)urea

N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethoxy)benzene]sulfonyl} benzamide

1-{[4-(benzenesulfonyl)phenyl]methyl}-3- (quinolin-6-yl)urea

3-{4-[(5-fluoro-2- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(benzenesulfonyl)phenyl]-1-{[6-(dimethylamino)pyridin-3-yl]methyl}urea

3-{4-[(4-chloro-2- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-fluoro-3- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2,3-difluorobenzene)sulfonyl] phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-chloro-6-fluoro-3- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-[4-(pyrimidine-5- sulfonyl)phenyl]urea

3-{4-[(3,5-difluorobenzene)sulfonyl] phenyl}-1-(pyridin-3-ylmethyl)urea

1-[6-(benzenesulfonyl)pyridin-3-yl]-3- (pyridin-3-ylmethyl)urea

3-{4-[(2,4-dichlorobenzene)sulfonyl] phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2,5-difluoro-4- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-[(3-aminophenyl)methyl]-3-[4- (benzenesulfonyl)phenyl]urea

3-{4-[(4-ethylbenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chlorobenzene)sulfinyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(2-chlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chloro-2- fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chlorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(5-fluoro-2- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-methoxybenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(4-fluorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-[4-(2-methoxynaphthalene-1- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{[({4-[(4- chlorobenzene)sulfonyl]phenyl}carbamoyl)amino]methyl}pyridin-1-ium-1-olate

3-{4-[(3-fluorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-[4-(2H-1,3-benzodioxole-5- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

4-[(2-chlorobenzene)sulfonyl]-N- {imidazo[1,2-a]pyridin-6-ylmethyl}benzamide

4-[(3-chlorobenzene)sulfonyl]-N- {imidazo[1,2-a]pyridin-6-ylmethyl}benzamide

3-{4-[(3-chlorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-(4-{[2- (methoxymethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-(benzenesulfonyl)phenyl]-1-{[6-(2-methoxyethoxy)pyridin-3-yl]methyl}urea

3-{4-[(2,3-dichlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(4-fluoro-2- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(2-phenoxybenzene)sulfonyl]phenyl}- 3-(pyridin-3-ylmethyl)urea

1-[4-(benzenesulfonyl)phenyl]-3- {5H,6H,7H,8H-imidazo[1,2-a]pyridin-6-ylmethyl}urea

3-(4-{[3-(propan-2- yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-acetylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-[4-(benzenesulfonyl)phenyl]-3- {imidazo[1,2-a]pyridin-6-ylmethyl}urea

3-{4-[(2,3- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-[4-(cyclopentanesulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-{4-[(2-fluoro-6- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea

3-[4-(benzenesulfonyl)phenyl]-1-(quinolin- 6-yl)urea

3-{4-[(2,5- dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-[4- (trifluoromethane)sulfonylphenyl]urea

3-{4-[(2-fluoro-4- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea

3-[4-(3,5-dimethyl-1,2-oxazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chloro-3- fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethyl)benzene]sulfonyl} benzamide

3-(4-{[2-chloro-5- (trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-fluorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

4-[(3,5-difluorobenzene)sulfonyl]-N- {imidazo[1,2-a]pyridin-6-ylmethyl}benzamide

1-(pyridin-3-ylmethyl)-3-(4-{[2- (trifluoromethyl)benzene]sulfonyl}phenyl)urea

3-(4-{[4-chloro-3- (trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(4- methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-fluoro-4- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[2-chloro-6-(propan-2-yl)pyridine-3-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-methoxy-5- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-[4-(pyridine-4- sulfonyl)phenyl]urea

N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-[(3-methoxybenzene)sulfonyl]benzamide

3-{4-[(2-chloro-4- fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-ethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(3-fluoro-4- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2,5-dichlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-[4-(pyridine-3- sulfonyl)phenyl]urea

3-{4-[(3-methylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(2,4-difluorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(2,6- dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(4-{8-oxatricyclo[7.4.0.0^(2,7)]trideca-1(9),2(7),3,5,10,12-hexaene-6-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-[4-(pyridine-2- sulfonyl)phenyl]urea

N-(1,3-benzothiazol-6-ylmethyl)-4-[(3- chlorobenzene)sulfonyl]benzamide

3-{4-[(5-chloro-2- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[2-methoxy-5-(propan-2- yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-(propan-2- yloxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[(2,4,6-trimethylbenzene)sulfonyl]phenyl}urea

3-{4-[(3-fluoro-4- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-methylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-[4-(benzenesulfonyl)phenyl]-3-{thieno[2,3- c]pyridin-2-ylmethyl}urea

3-{4-[(2,4- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(2,5-difluorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(2-fluoro-5- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[4- (trifluoromethoxy)benzene]sulfonyl]phenyl)urea

3-[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-[4-(5-methylthiophene-2-sulfonyl)phenyl]- 1-(pyridin-3-ylmethyl)urea

3-{4-[(3,4-difluorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

1-(4-benzoylphenyl)-3-(pyridin-3- ylmethyl)urea

3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3- yl)urea

3-{4-[(2,6- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

4-(benzenesulfonyl)-N-(pyridin-3- yl)benzamide

4-(benzenesulfonyl)-N-(pyridin-4- yl)benzamide

3-[4-(2-methoxypyrimidine-5- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(3-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-methoxy-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-(phenylsulfamoyl)phenyl]-3-(pyridin-3- ylmethyl)urea

3-{4-[(3-chloro-4- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{8-methyl-2,8-diazaspiro[5.5]undecane-2-sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{4-[4- (trifluoromethyl)phenyl]piperazine-1-sulfonyl}phenyl)urea

3-{4-[(3,4-difluorophenyl)sulfamoyl] phenyl}-1-(pyridin-3-ylmethyl)urea

N-methyl-5-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyridine-2-carboxamide

3-{4-[(2R)-2-(methoxymethyl)pyrrolidine-1-sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea

3-(4-{[3-fluoro-5-(2,2,2- trifluoroethoxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chloro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-(3-methoxyphenyl)pentan-3- yl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-fluoro-4- propoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[4-fluoro-3- (trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-methoxy-3- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[4-chloro-3- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[2-(morpholin-4-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea

1-[4-(3,5-dimethylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

(2S)-N,N-dimethyl-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] pyrrolidine-2-carboxamide

methyl 4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazine-1-carboxylate

3-{4-[(2- methoxyethyl)(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[4-(2H-1,3-benzodioxol-5-yl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-{4-[(2-methoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

N-(propan-2-yl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

3-(4-{[(2- methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-(1-methyl-1H-indole-2-sulfonyl)phenyl]- 1-(pyridin-3-ylmethyl)urea

3-{[4-(piperidine-1-sulfonyl)phenyl]methyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(2-fluoro-4- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-fluorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-[4-(cycloheptylsulfamoyl)phenyl]-3- (pyridin-3-ylmethyl)urea

1-{4-[4-(pyrazin-2-yl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-{4-[(5-methylpyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(2-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[(1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3- yl]sulfamoyl}phenyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{4-[6-(trifluoromethyl)pyridin-2-yl]piperazine-1- sulfonyl}phenyl)urea

3-{4-[(3-ethoxy-4- fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(2-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(6-ethylpyridin-2-yl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[3-(2-methoxyethyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-methoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

N-cyclopropyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

3-{4-[(4-methoxy-3,5- dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[2-methyl-4- (trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-{4-[4-(morpholin-4-yl)piperidine-1- sulfonyl]phenyl}urea

3-[4-(piperidine-1-sulfonyl)phenyl]-1- (pyrimidin-5-ylmethyl)urea

3-(4-{[2-(3- methoxyphenyl)ethyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

N-[(3R)-1-[(4-{[pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidin-3-yl]acetamide

1-{4-[(4-phenylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(2,4-difluorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-(4-{[3- (dimethylsulfamoyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-methoxy-6- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3- methanesulfonylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chloro-2- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

N-methyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperazin-1-yl}acetamide

3-{4-[(4-chloro-2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea

3-(4-{[3-chloro-5- (trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(1,5-dimethyl-1H-pyrazol-3- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-(2- methoxyethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(2,4-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{methyl[(1S)-1- phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-(4-{8-azaspiro[4.5]decane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-{4-[(5-chloro-2- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2,4-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(2,5-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

1-[4-(piperidine-1-sulfonyl)phenyl]-3-(pyridin- 3-ylmethyl)urea

1-{4-[(3S)-3-cyanopiperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-{4-[(2S)-2-(methoxymethyl)pyrrolidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{8-oxa-3-azabicyclo[3.2.1]octane-3- sulfonyl}benzamide

1-{4-[(5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)sulfamoyl]phenyl}-3-(pyridin-3- ylmethyl)urea

1-(4-{4-[2-(morpholin-4-yl)-2- oxoethyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

1-{4-[(3-benzoylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(6-methoxypyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-chloro-4- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

N-ethyl-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide

3-(4-{[4-(2- methoxyethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-(6-methoxynaphthalene-2-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[4-(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea

3-{4-[cyclohexyl(methyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(3-methoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-(4-{[4-(4- chlorophenoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-ethylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-[4-({4-[(pyrrolidin-1-yl)carbonyl]benzene}sulfonyl)phenyl]urea

3-(4-{[3-(2- hydroxyethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-chloro-2,6- dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(2,5-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(3-methylpiperidine-1-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea

3-{4-[4-(4-bromophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-methylpyridin-4- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(5-fluoro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-[(3,4-difluorophenyl)methyl]-3-[4- (piperidine-1-sulfonyl)phenyl]urea

4-(piperidine-1-sulfonyl)phenyl N-(pyridin-3- ylmethyl)carbamate

3-{4-[(4-methoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-(4-{4-[2-(3,4- dichlorophenyl)acetyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-({2-[(2S)-2- hydroxypropoxy]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea

1-[4-(1H-indole-7-sulfonyl)phenyl]-3-(pyridin- 3-ylmethyl)urea

3-{4-[(3-chloro-5- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[4- (ethoxymethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-{4-[(1- phenylcyclopentyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[3- (trifluoromethyl)piperidine-1-sulfonyl]phenyl}urea

1-{4-[(3-phenylbenzene)sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(3,4-dichlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

1-{4-[(pyridin-2-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

(3S)-N,N-diethyl-1-[(4-{(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperidine-3-carboxamide

3-(pyridin-3-ylmethyl)-1-[4-(quinoline-6- sulfonyl)phenyl]urea

1-(4-{[(1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl]sulfamoyl}phenyl)-3-(pyridin-3- ylmethyl)urea

3-[(5-chloropyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea

3-{4-[4-(3-chlorophenyl)-4-cyanopiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(4-methanesulfonylpiperazine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-[4-(1H-pyrrole-1- sulfonyl)phenyl]urea

3-{4-[(4-ethoxy-2- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-propylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[4-cyano-4-(4-methoxyphenyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea

3-(4-{[(4- chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-[3-(piperidine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-{4-[4-(3-fluorophenoxy)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(pyridin-3-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-[4-(thiomorpholine- 4-sulfonyl)phenyl]urea

3-(4-{[2-chloro-5- (trifluoromethoxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-[4-(pyrrolidine-1- sulfonyl)phenyl]urea

2-methyl-N-{3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]phenyl}propanamide

1-[4-(cyclohexylsulfamoyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-[4-(piperidine-1-sulfonyl)phenyl]-1-[1- (pyridin-3-yl)ethyl]urea

1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-4-carboxamide

3-{4-[(2-tert-butylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-(4-{[(4- methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-chloro-5- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[4-fluoro-3- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-(4-{3-[(2-oxopyrrolidin-1- yl)methyl]piperidine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

1-(4-{[2-(morpholin-4- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[(2,4,6-trimethylphenyl)sulfamoyl]phenyl}urea

3-[4-(piperidine-1-sulfonyl)phenyl]-1-[2- (pyridin-3-yl)ethyl]urea

1-[4-(4-cyclohexylpiperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

3-{4-[(2-chloro-4- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(5-fluoro-2- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(methylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea

1-[4-(phenoxathiine-4-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-{4-[(3,5-dichlorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

1-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6- ylmethyl}urea

N-(propan-2-yl)-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperazin-1-yl}acetamide

N,N-diethyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperazin-1-yl}acetamide

3-(pyridin-3-ylmethyl)-1-[4-(quinoline-8- sulfonyl)phenyl]urea

1-(4-{[4-(piperidin-1- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-{4-[4-(3,5-dichloropyridin-4-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl) urea

1-[4-(cyclobutylsulfamoyl)phenyl]-3-(pyridin- 3-ylmethyl)urea

3-[4-(4-methylpiperidine-1-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{4-[4-(trifluoromethyl)pyridin-2-yl]piperazine-1- sulfonyl]phenyl)urea

1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

1-[4-(4-benzyl-1,4-diazepane-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

N-[(3S)-1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidin-3-yl]acetamide

3-(pyridin-3-ylmethyl)-1-[4-(quinoline-3- sulfonyl)phenyl]urea

3-(4-{[3-fluoro-5-(2- methylpropoxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

N,N-dimethyl-2-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide

1-{4-[(3-cyanobenzene)sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-[(5-fluoropyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea

1-{4-[(2H-1,3-benzodioxol-5- yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea

1-[4-(isoquinoline-4-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-{4-[(2-chloro-4-methylphenyl) sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(4-{3-azaspiro[5.5]undecane-3- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-{4-[4-(2,4-difluorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(diethylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea

N-(2-methylpropyl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

3-(4-{[3- (difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(4-{[2-methoxy-5- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(2-ethoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

N-ethyl-4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide

3-[4-(6-methoxypyridine-3-sulfonyl)phenyl]- 1-(pyridin-3-ylmethyl)urea

3-(4-{[3-(propan-2- yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-{4-[(3-phenylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-(4-{[(3- fluorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-propoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[4- (trifluoromethyl)piperidine-1-sulfonyl]phenyl}urea

3-{4-[(3-ethylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-(4-{[4-(propan-2- yloxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-[4-(benzylsulfamoyl)phenyl]-3-(pyridin-3- ylmethyl)urea

3-{4-[(4-ethoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(2-methoxypyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-[4-(4,4-difluoropiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

3-{4-[(3S)-3-methyl-4-(4- methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

1-{4-[4-(piperidin-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-[4-(butylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea

3-{4-[(5-methylpyridin-2- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3,4- dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(3-cyanophenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(3-chlorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-[4-(dimethylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea

3-{4-[methanesulfonyl(piperidin-4- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{4-[(4-fluorophenyl)carbonyl]piperidine-1-sulfonyl}phenyl)-1-(pyridin- 3-ylmethyl)urea

3-{4-[(3S)-4-(4-methoxyphenyl)-3- methylpiperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[(3S)-3- (trifluoromethyl)piperidine-1-sulfonyl]phenyl}urea

3-{4-[methyl(oxolan-3-yl)sulfamoyl] phenyl}-1-(pyridin-3-ylmethyl)urea

1-[4-(2,3-dihydro-1-benzofuran-7-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

3-{4-[4-(2-methoxyethyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-[4-(2,3-dihydro-1,4-benzodioxine-6-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

3-(4-{[4- (difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-methyl-4-(propan-2- yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[methyl({[5-(trifluoromethyl)pyridin-2-yl]methyl})sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea

1-(4-{4-[3-(morpholin-4-yl)propyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-(4-{[3-(propane-1- sulfonamido)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-{4-[(2,3-dihydro-1,4-benzodioxin-6- yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-{4-[4-(5-chloro-2-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(naphthalen-1-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-(4-{[3-chloro-4- (trifluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-{4-[4-(2H-1,3-benzodioxol-5- ylmethyl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

N-methyl-N-phenyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperazin-1-yl}acetamide

1-(4-{4-[(furan-2-yl)carbonyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-{4-[4-(5-chloro-2- methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(propan-2-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(5-fluoropyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(2-methyl-3-oxopiperazine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-ethoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[4-(2,6-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-chlorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-[4-(1H-indole-4-sulfonyl)phenyl]-3-(pyridin- 3-ylmethyl)urea

3-chloro-N,N-diethyl-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

3-[2-fluoro-4-(piperidine-1-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea

N,N-dimethyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

1-(pyridin-3-ylmethyl)-3-[4-({[3-(trifluoromethyl)phenyl]methyl}sulfamoyl) phenyl]urea

pyridin-3-ylmethyl N-[4-(piperidine-1- sulfonyl)phenyl]carbamate

1-(4-{[3-(piperidin-1- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-(4-{[2-(2- hydroxyethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-benzyl-1-[4-(piperidine-1- sulfonyl)phenyl]urea

3-{4-[(2- hydroxyethyl)(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[4-(trifluoromethane)sulfonylphenyl]sulfamoyl} phenyl)urea

3-{4-[(4-chlorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(3- ethanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(4-chloro-3- methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-methylpropyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

N-(2-hydroxyethyl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

3-{4-[(3-chloro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-fluoro-4- (trifluoromethoxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-chloro-4- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[4-fluoro-3-(2,2,2- trifluoroethoxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-[4-(morpholine-4-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-(4-{[(4-chlorophenyl) methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[methyl(2-methylpropyl) sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chlorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-(4-{methyl[(1R)-1- phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(2-chlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-({2-[(1S)-1- hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-{4-[(quinolin-6- yl)sulfamoyl]phenyl}urea

3-{4-[(2,5-difluorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

1-(4-{[2-(piperidin-1- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-{4-[(3-tert-butylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-(4-{methyl[2-(4- methylphenyl)ethyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2,6-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[(1,3,5-trimethyl-1H-pyrazol-4-yl)sulfamoyl]phenyl}urea

1-(4-{3-azatricyclo[7.3.1.0^(5,13)]trideca-1(13),5,7,9,11-pentaene-3-sulfonyl}phenyl)-3- (pyridin-3-ylmethyl)urea

N,N-dimethyl-2-{4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonamido]phenyl}acetamide

3-[(6-chloropyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea

3-(4-{[(5-methylfuran-2- yl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-(4-{4-[2-oxo-2-(piperidin-1- yl)ethyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-[4-(3,3,5-trimethylazepane-1-sulfonyl)phenyl]urea

3-(4-{[3-(3,5-dimethyl-1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea

3-(4-{[3- (methoxymethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-fluoro-5- (trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-(4-{[2-(morpholin-4- ylmethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

N-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-4-(1,2,3,4-tetrahydroisoquinoline-2- sulfonyl)benzamide

methyl 4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzoate

3-(4-{[2-(propan-2- yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-(propan-2- yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-fluoro-4-(2,2,2- trifluoroethoxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[(3,4,5-trifluorophenyl)sulfamoyl]phenyl}urea

1-{4-[(pyridin-2-ylmethyl)sulfamoyl]phenyl}- 3-(pyridin-3-ylmethyl)urea

N,N-diethyl-4-fluoro-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

1-(4-{[4-(piperidine-1- sulfonyl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-{4-[(2,4-dichlorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-(4-{[3- (ethylsulfamoyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-[4-(4-cyanopiperidine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-{4-[(2,2-dimethylpropyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

1-[4-(dibenzylsulfamoyl)phenyl]-3-(pyridin-3- ylmethyl)urea

(2S)-1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidine-2-carboxamide

1-(4-{3-oxa-8-azabicyclo[3.2.1]octane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

1-{4-[(1H-indazol-5-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

tert-butyl N-{5-[({[4-(piperidine-1-sulfonyl)phenyl]carbamoyl}amino)methyl] pyridin-2-yl}carbamate

3-{4-[benzyl(methyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[4-(3-chloropyridin-2-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[2-(propan-2- yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(3- methanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

N,N-diethyl-3-fluoro-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

3-(4-{[4- (methoxymethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

N,N-dimethyl-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperidine-4-carboxamide

3-{4-[(propan-2-yl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-[4-({3-[(morpholin-4- yl)carbonyl]benzene}sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

3-(4-{[(4- fluorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-ethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[benzyl(propan-2-yl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-[4-({[4- (dimethylamino)phenyl]methyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[benzyl(ethyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(4-acetylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-[4-(4-{[(2R)-oxolan-2- yl]carbonyl}piperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

2-methyl-N-{1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperidin-4-yl}propanamide

1-(pyridin-3-ylmethyl)-3-(4-{[4- (trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea

3-(pyridin-3-ylmethyl)-1-(4-{[4-(pyrrolidin-1-yl)phenyl]sulfamoyl}phenyl)urea

3-(4-{[(3- chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(4-{[3- (ethanesulfonyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-(4-hydroxypiperidine-1-sulfonyl)phenyl]- 1-(pyridin-3-ylmethyl)urea

3-(4-{[3- (hydroxymethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-acetylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(3-ethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

4-fluoro-N-(propan-2-yl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

3-{4-[4-(3-chlorophenyl)-4-hydroxypiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3S)-3-methyl-4-(3- methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chloro-3- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2,3-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[4-(2,3-dichlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-[4-(4-benzylpiperidine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea

1-(4-{[(4- phenylphenyl)methyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-{4-[(5,6,7,8- tetrahydronaphthalen-1-yl)sulfamoyl]phenyl}urea

rel-3-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-[4-(decahydroquinoline-1-sulfonyl)phenyl]- 3-(pyridin-3-ylmethyl)urea

3-{4-[(4-fluoro-2- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(4-ethynylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(3-chloro-4- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-chloro-4,6- dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-fluoro-4- (trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-{4-[(2R)-2-benzylpiperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrazin- 2-ylmethyl)urea

3-{4-[(4-fluoro-3- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)sulfamoyl]phenyl}-3-(pyridin-3- ylmethyl)urea

3-{4-[4-(diethylamino)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4- fluorophenyl)(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(2-methylpyridine-3-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea

1-{4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-{4-[(3-fluoro-5- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4-{3-oxa-8-azabicyclo[3.2.1]octane-8- sulfonyl}phenyl)urea

3-{4-[(3-fluoro-4- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-methylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

rel-3-{4-[(4aR,8aS)-decahydroisoquinoline-2-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(4-methanesulfonylpiperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-{4-[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1- sulfonyl]phenyl}urea

3-{4-[(6-methylpyridin-2- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{4-[(morpholin-4-yl)carbonyl]piperidine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[3-(2-chloro-4-fluorophenoxy)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{4-[4-chloro-3- (trifluoromethyl)phenyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(4-{[3-(2- methylpropoxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(4-{4-[bis(4-fluorophenyl)methyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

1-(4-{[3- (benzyloxy)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-(4-{[3-(pyrrolidin-1-yl)phenyl]sulfamoyl}phenyl)urea

3-{4-[(4-ethoxy-3- fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3,5-dichlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[4-(3,4-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[3- (trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea

3-{4-[(2-ethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(3- methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-methoxy-4- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(6-methylpyridine-3-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-[4-(5,6,7,8- tetrahydro-1,6-naphthyridine-6-sulfonyl)phenyl]urea

3-[4-(2,4-dimethoxypyrimidine-5-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[(5-methoxy-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[4-(propan-2- yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(5-chloro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[(2-fluorophenyl)methyl]-1-[4-(piperidine-1- sulfonyl)phenyl]urea

3-(4-{[2-(4-fluorophenoxy)pyridin-3- yl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-{4-[(4-phenoxyphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-{4-[(pyridin-4- ylmethyl)sulfamoyl]phenyl}urea

1-{4-[4-(azepan-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

1-(4-{[4-(1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

1-{4-[(cyclohexylmethyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(4-ethylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(4-bromophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-[(6-aminopyridin-3-yl)methyl]-1-[4- (piperidine-1-sulfonyl)phenyl]urea

3-{4-[(3,4-dichlorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(4-tert-butylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

1-{4-[4-(2-oxo-2,3-dihydro-1H-indol-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3- ylmethyl)urea

1-[(6-isocyanopyridin-3-yl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea

3-(4-{[2-(3- chlorophenyl)ethyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-fluoro-3- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(4-{[3-(1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-{4-[3-(pyrrolidin-1-yl)pyrrolidine-1-sulfonyl]phenyl}urea

1-[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]- 3-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[3-(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea

3-{4-[methyl(2- phenylethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-[4-(3,4-dihydro-2H-1,4-benzoxazine-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

3-{4-[(3S)-3-methylpiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-[(4-fluorophenyl)methyl]-3-[4-(piperidine-1- sulfonyl)phenyl]urea

3-[4-(tert-butylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea

1-[4-(4-phenylpiperazine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-{4-[4-(5-methylpyrimidin-2-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(azepane-1-sulfonyl)phenyl]-1-(pyridin-3- ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[2-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea

3-(4-{[3-chloro-4- (trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-acetylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(4-methylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[4-(4-bromo-3- methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(piperidine-1-sulfonyl)phenyl]-1-{[6-(trifluoromethyl)pyridin-3-yl]methyl}urea

3-[4-(5-fluoropyridine-3-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea

1-(4-{2-oxa-8-azaspiro[4.5]decane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

1-{4-[4-(2-phenylacetyl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

1-{4-[4-(3-phenylprop-2-en-1-yl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[(3- sulfamoylbenzene)sulfonyl]phenyl}urea

N-methyl-2-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide

3-(4-{[4-(propan-2- yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-hydroxyethyl)(propan-2- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(adamantan-1-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

1-{4-[(2R)-2-(morpholin-4- ylmethyl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-{4-[4-(3,5-dichlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-fluoro-5- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

N-{3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]phenyl}acetamide

N-methyl-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide

3-{4-[4-(4-chlorophenyl)-4-cyanopiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[4-methyl-3- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-[4-(4-phenylpiperidine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-{4-[(3-acetylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[4-(methoxymethyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-fluoro-N,N-dimethyl-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

N-[2-(pyridin-3-yl)ethyl]-4-{[3-(trifluoromethoxy)phenyl]sulfamoyl}benzamide

3-{4-[cyclohexyl(ethyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[4-(3,4-dichlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-fluoro-3- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[2-fluoro-5- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-(4-{[4-(propan-2- yl)phenyl]methyl}piperazine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{4-[3- (trifluoromethyl)phenyl]piperazine-1-sulfonyl}phenyl)urea

1-[4-(cyclopropylsulfamoyl)phenyl]-3- (pyridin-3-ylmethyl)urea

4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-[2-(pyridin-3-yl)ethyl]benzamide

3-{4-[(3- aminophenyl)(methanesulfonyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(2,3-dihydro-1H-inden-5- yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-(4-{[3-chloro-4-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea

3-{4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{4-[1-(3-methoxyphenyl)-4- methylcyclohexyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(4-{[(5-ethylpyridin-2- yl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-chloro-4- propoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chloronaphthalen-1- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(5-acetyl-2- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(5-chloro-2- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine]-1′-ylsulfonyl]phenyl}-3-(pyridin- 3-ylmethyl)urea

3-{4-[4-(2,4-dimethoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{[4-(piperidine-1-sulfonyl)phenyl]methyl}- 1-(pyridin-3-yl)urea

N-{1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidin-4-yl}acetamide

3-(4-{[3- (methoxymethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-fluoro-4- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(2-phenylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

1-(4-{4-[(2-oxopyrrolidin-1- yl)methyl]piperidine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-(4-{[2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea

3-(4-{[2-methoxy-5- (trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-[4-(2,6-dimethylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea

1-{4-[(1-phenylcyclohexyl)sulfamoyl]phenyl}- 3-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[6- (trifluoromethyl)pyridine-3-sulfonyl]phenyl}urea

3-{4-[(4-methylpyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(2-methylpropyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(4-{4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]piperazine-1-sulfonyl}phenyl)-3- (pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-{4-[(4- sulfamoylphenyl)sulfamoyl]phenyl}urea

5-[({[4-(piperidine-1- sulfonyl)phenyl]carbamoyl}amino)methyl]pyridine-2-carboxamide

3-(4-{4-[(4-tert- butylphenyl)methyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-(azetidine-1-sulfonyl)phenyl]-1-(pyridin- 3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-(4-{[2-(1H-pyrrol-1-yl)phenyl]sulfamoyl}phenyl)urea

3-(4-{4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazine-1-sulfonyl]phenyl)-1-(pyridin-3- ylmethyl)urea

N,N-diethyl-2-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide

1-{4-[(piperidin-1-yl)carbonyl]phenyl}-3- (pyridin-3-ylmethyl)urea

N-ethyl-N-[(3S)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] pyrrolidin-3-yl]acetamide

3-(pyridin-3-ylmethyl)-1-{4-[4-(pyrimidin-2-yl)piperazine-1-sulfonyl]phenyl}urea

3-{4-[(3-ethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[3-chloro-2-(morpholin-4-yl)pyridine-4-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-(4-{[(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan-3- yl]sulfamoyl}phenyl)urea

3-{4-[(4-fluoro-3- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-phenylpropan-2- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{4-[(1R)-1-(4- chlorophenyl)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-[4-(5-chloropyridine-3-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea

3-[(3-fluorophenyl)methyl]-1-[4-(piperidine-1- sulfonyl)phenyl]urea

3-{4-[4-cyano-4-(4-methylphenyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(3-phenoxyphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(2,5- dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-fluoro-5- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-methoxy-5- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-{4-[(pyridin-3- ylmethyl)sulfamoyl]phenyl}urea

3-{4-[4-(dipropylamino)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-methylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-(4-{[(4-fluorophenyl) methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-{4-[(3S)-3-[(pyrrolidin-1-yl)carbonyl]piperidine-1- sulfonyl]phenyl}urea

3-{4-[(3-bromophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-{4-[(2-phenoxyphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-(4-{4-[1-(4-chlorophenyl)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

N,N-dimethyl-4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide

1-{4-[(4-phenylbenzene)sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(3,5-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[4-(4-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(4-acetyl-1,4-diazepane-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

N-cyclopentyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

3-[4-(3,3-difluoroazetidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

1-(4-{[4-(morpholin-4- yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-[4-({3-[(1S)-1- hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[(3,5-ditluorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(3,5- dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[ethyl(phenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{[2-(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea

3-(4-{[3-(5-methyl-1,3,4-oxadiazol-2-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea

3-[4-({4-[(1S)-1- hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-methoxy-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

4-[(3-chlorophenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide

3-{4-[(4-tert-butyl-2- chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(4-{8-azabicyclo[3.2.1]octane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

1-[4-(cyclopentylsulfamoyl)phenyl]-3- (pyridin-3-ylmethyl)urea

3-(4-{4-[2-(diethylamino)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(4-chlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[2-(3- fluorophenyl)ethyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[methyl({[3- (trifluoromethyl)phenyl]methyl})sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(4-{[3-(morpholin-4- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-(4-{[(2- chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-(4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-{4-[4-(4-acetylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(1H-indazol-6-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[4-(3,4-dimethoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

N,N-dimethyl-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide

1-(4-{[3- (cyclopropylmethoxy)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

(2R)-1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidine-2-carboxamide

3-(4-{[(3- methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2-methylpyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-[4-(ethylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea

3-{4-[(2-fluorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-(4-{[2- (difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

1-(4-{2-azabicyclo[2.2.1]heptane-2-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea

3-{4-[(3,5-dimethyl-1,2-oxazol-4- yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(pyridin-3-ylmethyl)-3-(4-{4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1- sulfonyl}phenyl)urea

3-[4-(2,3-dihydro-1H-indole-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-acetylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(4-fluoro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-{4-[(4-cyanophenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(3-chloro-4- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(3-chloro-5- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(4-(4-((2- methoxyethyl)(methyl)amino)piperidin-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

3-{4-[(2,4- dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(pyridin-3-ylmethyl)-1-(4-{[2-(pyrrolidin-1-yl)phenyl]sulfamoyl}phenyl)urea

3-{4-[(3-methoxy-4- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(4-nitrophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(2-chloro-4-fluorophenoxy)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-(4-{[4-chloro-2- (trifluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-chloro-3- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2,3-dichlorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-(4-{[4-(propan-2- yl)benzenelsulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4-{8-oxa-3-azabicyclo[3.2.1]octane-3- sulfonyl}phenyl)urea

2-fluoro-N-(propan-2-yl)-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide

3-(4-{[2-(2- hydroxyethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea

3-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(4-fluoro-2- methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[4-(3-chlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

3-{4-[(2S)-2-ethylpiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea

1-(4-{[4-(morpholin-4- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea

1-{4-[(4-cyanobenzene)sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea

3-{4-[(2-bromophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

3-{4-[(3,4-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea

3-{4-[(2-iodophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

1-{4-[2-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea

3-{4-[(3-fluorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea

N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethoxy)phenyl]sulfamoyl}benzamide

1-[4-(piperazine-1-sulfonyl)phenyl]-3-(pyridin- 3-ylmethyl)urea

4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide

The following compounds are not compounds of the invention but are NAMPTinhibitors:

The disclosures in this application of all articles and references,including patents and patent applications are incorporated herein byreference.

EXAMPLES

The invention is illustrated further by the following examples, whichare not to be construed as limiting the invention in scope or spirit tothe specific procedures described in them. Those having skill in the artwill recognize that the starting materials may be varied and additionalsteps employed to produce compounds encompassed by the presentinventions, as demonstrated by the following examples.

In some cases, protection of certain reactive functionalities may benecessary to achieve some of the above transformations. In general, suchneed for protecting groups, as well as the conditions necessary toattach and remove such groups, will be apparent to those skilled in theart of organic synthesis. Unless otherwise specified, all reagents andsolvents are of standard commercial grade and are used without furtherpurification.

The following are illustrative, but non-limiting, examples of certainembodiments of the present invention.

Definitions Used in the Following Schemes and Elsewhere Herein are

-   CDCl₃ deuterated chloroform-   6 chemical shift (ppm)-   DCM dichloromethane or methylene chloride-   DIEA N, N-diisopropylethylamine-   DMA N, N-dimethylacetamide-   DMAP N, N-dimethylpyridin-4-amine-   DMF dimethylformamide-   DMSO dimethylsulfoxide-   DMSO-d₆ deuterated dimethylsulfoxide-   EDCI N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine    hydrochloride-   EtOAc ethyl acetate-   EtOH ethanol-   GF/F glass microfiber filter-   ¹H NMR proton nuclear magnetic resonance-   HOAc acetic acid-   HATU    2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium    hexafluorophosphate-   HOBT 1H-benzo[d][1,2,3]triazol-1-ol hydrate-   HPLC high pressure liquid chromatography-   MHz megahertz-   KOAc potassium acetate-   i-PrOH isopropanol-   LC-MS liquid chromatography/mass spectrometry-   (M+1) mass+1-   m-CPBA m-chloroperbenzoic acid-   MeOH methanol-   N₂ nitrogen-   NaHCO₃ sodium bicarbonate-   MgSO₄ magnesium sulfate-   SRB Sulforhodamine B colorimetric assay-   TEA triethylamine-   THF tetrahydrofuran-   TLC thin layer chromatography

Preparation of Compounds

The compounds of the present invention can be prepared through numerousroutes well-known to those skilled in the art of organic synthesis. Byway of example, compounds of the present invention can be synthesizedusing the methods described below, together with synthetic methods knownin the art of synthetic organic chemistry, or variations thereon asappreciated by those skilled in the art. Preferred methods include butare not limited to those methods described below.

Compounds of the present invention urea-sulfonamide (IV) can besynthesized by following the steps outlined in Scheme 1.

Intermediate II can be obtained by treating I with phosgene,thiophosgene, carbonyldiimidazole, or other such activating group in aninert solvent such as dichloromethane, benzene, or toluene attemperatures ranging from −78° C. to 200° C. Intermediate V can beobtained by treating I with 4-nitrophenyl carbonochloridate in an inertsolvent such as dichloromethane, benzene, or toluene at temperaturesranging from −78° C. to 200° C. The compound of present invention IV canbe obtained by treating compound III with either II or V in an organicsolvent at temperatures ranging from −78° C. to 200° C.

Compounds of the present invention urea-sulfone (IV) can be synthesizedby following the steps outlined in Scheme 2.

Intermediate II can be obtained by treating I with phosgene,thiophosgene, carbonyldiimidazole (or similar reagent) in an inertsolvent such as dichloromethane, benzene, or toluene at temperaturesranging from −78° C. to 200° C. The compound of present invention IV canbe obtained by treating intermediate II with III in an organic solventat temperatures ranging from −78° C. to 200° C.

The compound of present invention urea-sulfone IV can also besynthesized by following the steps outlined in Scheme 2A.

Intermediate VI can be obtained by treating III with V in an inertsolvent such as dichloromethane and benzene at temperatures ranging from−78° C. to 200° C. Treatment of VI with agents such as NaBH₄, NaI, orNa₂S₂O₃ in a solvent such as water or THF at temperatures ranging from−78° C. to 200° C. gives intermediate VII. Compound IV can be obtainedby treating VII and VIII with a suitable transition metal catalyst suchas, but not limited to, Pd(PPh₃)₄, palladium(II) acetate, or Cu(OAc)₂ inthe presence of a base (eg: K₂CO₃, Cs₂CO₃, NR₁R₂R₃, NaOR, KOR) in aninert solvent such as N, N-dialkylformamide, N, N-dialkylacetamide, ordichloromethane at temperatures ranging from −78° C. to 200° C.

Those having skill in the art will recognize that the starting materialsmay be varied and additional steps may be employed to produce thecompounds encompassed by the present inventions (as demonstrated by thefollowing examples). Unless otherwise specified, all reagents andsolvents are of standard commercial grade and are used without furtherpurification.

The disclosures in this application of all articles and references,including patents, are incorporated herein by reference.

Preparation of Representative Urea-Sulfonamide and Urea Sofone Analogues

These examples illustrate the preparation of representative substitutedurea-sulfonamide and urea-sulfone analogues.

Example 1

1-((5-fluoropyridin-3-yl)methyl)-3-(4-(piperidin-1-ylsulfonyl)phenyl)urea

Triphosgene (41 mg, 0.137 mmol) was dissolved in DCM (5 mL) and cooledto −10° C. under N₂ atmosphere. To this cooled solution was addeddropwise a mixture of 4-(piperidin-1-ylsulfonyl) aniline (100 mg, 0.416mmol) and TEA (127 mg, 1.25 mmol) in DCM (5 mL). The mixture was stirredat −10° C. for 5 minutes and allowed to warm up to room temperature for1 hour. A solution of 5-fluoropyridin-3-yl)methanamine (55 mg, 0.50mmol) and TEA (127 mg, 1.25 mmol) in DCM (5 mL) was then added. Thereaction mixture was stirred at room temperature for 16 hours. Themixture was diluted with DCM (25 mL), washed with brine (2×15 mL), driedover MgSO₄, filtered and concentrated under reduced pressure. The crudewas purified by Biotage using 5% MeOH/DCM to afford the desired productas a white amorphous powder.

¹H NMR (300 MHz, CDCl₃): δ 9.23 (s, 1H), 8.36-8.48 (m, 2H), 7.50-7.68(m, 5H), 6.95 (t, 1H), 4.36 (d, 2H), 2.75-2.90 (m, 4H), 1.48-1.75 (m,4H), 1.38-1.42 (m, 2H) LC-MS: 393.04 (M+1).

Example 2

N-(naphthalen-1-yl)-4-(3-(pyridin-3-ylmethyl)ureido)benzenesulfonamide

A: N-(naphthalen-1-yl)-4-nitrobenzenesulfonamide:

To a cooled solution of naphthalen-1-amine (2000 mg, 13.97 mmol) inpyridine (45.0 mL) was added DMAP (171 mg, 1.4 mmol) and a solution of4-nitrobenzene-1-sulfonyl chloride (3410 mg, 15.4 mmol) in pyridine(15.0 mL) at 0° C. The mixture was stirred at 0° C. for 15 min andheated to 80° C. for 16 h. After being cooled to room temperature, themixture was acidified with 2 M HCl, extracted with EtOAc (3×50 mL),washed several times with brine, dried over MgSO₄ and concentrated invacuo. The crude was purified by Combiflash using (5% EtOAc/hexanes) toafford the title compound.

¹H NMR (300 MHz, CD₃OD): δ 7.21-7.38 (m, 6H), 7.68-7.85 (m, 4H),8.15-8.20 (m, 2H).

LC-MS: 329.14 (M+1).

B: 4-amino-N-(naphthalen-1-yl)benzenesulfonamide:

A mixture of N-(naphthalen-1-yl)-4-nitrobenzenesulfonamide (3.9 g, 12mmol) and tin (II) chloride dihydrate (13.5 g, 60 mmol) was refluxed inEtOAc (120 mL) for 2.5 h. After being cooled to room temperature, themixture was treated with 2N NaOH (100 mL) and stirred for 1 h, thenfiltered through celite and washed with EtOAc. The combined filtrateswere concentrated in vacuo. The crude was purified by Combiflash using(40% EtOAc/hexanes) to afford the title compound.

¹H NMR (300 MHz, CD₃OD): δ 6.45-6.51 (m, 2H), 7.12-7.18 (m, 1H),7.25-7.38 (m, 5H), 7.65 (d, 1H), 7.72-7.76 (m, 1H), 7.91-7.98 (m, 1H).

LC-MS: 299.04 (M+1).

C:N-(naphthalen-1-yl)-4-(3-(pyridin-3-ylmethyl)ureido)benzenesulfonamide:

A mixture of 4-amino-N-(naphthalen-1-yl)benzenesulfonamide (1000 mg,3.35 mmol) and 4-nitrophenyl carbonochloridate (676 mg, 3.35 mmol) inDCM (35 mL) was stirred and cooled to 0° C. under N₂ atmosphere,followed by addition of pyridine (1060 mg, 13.41 mmol). After beingstirred for 10 minutes, pyridin-3-methanamine (1087 mg, 10.5 mmol) wasadded and the reaction mixture was stirred for 40 minutes at roomtemperature. The mixture was then diluted with DCM-MeOH (100 mL, 1:1),washed with water (5×40 mL), dried over MgSO₄, and concentrated undervacuum. The residue was purified by flash chromatography using 10%MeOH/DCM to afford the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ 4.21 (d, 2H), 6.82-6.88 (m, 1H), 7.10-7.16(m, 1H), 7.32-7.55 (m, 8H), 7.58-7.68 (m, 2H), 7.85-7.89 (m, 1H),8.05-8.10 (m, 1H), 8.40-8.46 (m, 1H), 8.52 (s, 1H), 9.08 (s, 1H), 10.08(s, 1H).

LC-MS: 433.25 (M+1). Example 3

1-(4-(4,4-difluoropiperidin-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

A: 4-(3-(pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride:

To an ice-cooled solution of 4-isocyanatobenzene-1-sulfonyl chloride (6g, 27.6 mmol) in THF (250 mL) was added pyridin-3-ylmethanamine (2.79mL, 27.6 mmol). The mixture was allowed to slowly warm to roomtemperature over 16 hours. The resulting precipitates were filtered off.The filtrate was concentrated to half volume and then treated with 200mL of anhydrous ether. The resulting precipitates were filtered again,and the mother liquor was treated with 200 mL of anhydrous ether. Thecombined precipitates were collected as the title compound and used fornext step without further purification.

¹H NMR (300 MHz, CDCl₃): δ 4.54 (s, 2H), 7.21 (br s, 1H), 7.33 (d, 2H),7.47 (d, 2H), 8.08 (dd, 1H), 8.55 (dt, 1H), 8.50 (m, 2H), 9.24 (s, 1H).B:1-(4-(4,4-difluoropiperidin-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea:

To an ice-cooled solution of 4,4-difluoropiperidine hydrochloride (2 g,12.69 mmol) and triethylamine (4.72 mL, 33.8 mmol) in anhydrousdichloromethane (100 mL) was added4-(3-(pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride (4.24 g,8.46 mmol) in one portion. The mixture was stirred at 0° C. for 5minutes and at room temperature for 16 hours. The mixture was dilutedwith methylene chloride and washed successively with saturated aqueoussodium bicarbonate, water, and saturated aqueous sodium chloride. Theorganic extract was dried over MgSO₄, filtered and concentrated undervacuum. The crude was purified by Biotage using 10% MeOH/DCM to give thetitle compound.

¹H NMR (300 MHz, DMSO-d₆): δ 2.05 (m, 4H), 3.02 (t, 4H), 4.33 (d, 2H),6.93 (t, 1H), 7.36 (dd, 1H), 7.64 (m, 4H), 7.71 (m, 1H), 8.46 (d, 1H),8.53 (s, 1H), 9.24 (s, 1H);

LC-MS: 410.40 (M+1)

Anal. Calcd. for C₁₈H₂₀F₂N₄O₃S: C, 52.67; H, 4.91; N, 13.65; F, 9.26; S,7.81.

Found: C, 52.44; H, 4.85; N, 13.49; F, 9.26; S, 7.53. Example 4

1-(4-(4-morpholinopiperidine-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

A: 4-(1-(4-nitrophenylsulfonyl)piperidin-4-yl)morpholine:

To an ice-cooled solution of 4-nitrobenzene-1-sulfonyl chloride (4 g,18.05 mmol) in DCM (50 mL) was added a solution of4-piperidin-4-yl)morpholine (3.69 g, 21.66 mmol) and TEA (3.77 mL, 27.1mmol) in DCM (920 mL). The mixture was stirred at 0° C. for 15 minutesand at room temperature for 16 hours. The mixture was diluted with DCM,washed with 1 M NaOH, brine, dried over Na₂SO₄ and concentrated invacuo. The residue was treated with ether and the resulting precipitateswere collected to give the title compound.

¹H NMR (300 MHz, CDCl₃): δ 8.32-8.39 (m, 2H), 7.89-7.97 (m, 2H), 3.84(d, 2H), 3.60-3.71 (m, 4H), 2.15-2.50 (m, 6H), 2.09-2.19 (m, 1H),1.85-1.92 (m, 2H), 1.50-1.70 (m, 2H)

LC-MS: 356.06 (M+1).

B: 4-(4-morpholinopiperidine-1-ylsulfonyl)aniline:

A mixture of 4-(1-(4-nitrophenylsulfonyl)piperidin-4-yl)morpholine (6.2g, 17.44 mmol) and Raney Ni (1.02 g) in HOAc (50 mL) was hydrogenatedfor 16 h at 50 psi. The reaction mixture was filtered and the filtratewas concentrated. The residue was suspended in water (50 mL) andneutralized with saturated aqueous NaHCO₃. The precipitate was collectedand dried under reduced pressure to afford the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ 7.21 (d, 2H), 6.61 (d, 2H), 6.03 (br s, 2H)3.45-3.65 (m, 6H), 2.30-2.41 (m, 4H), 1.95-2.17 (m, 3H), 1.69-1.79 (m,2H), 1.30-1.45 (m, 2H)

LC-MS: 326.07 (M+1)

C:1-(4-(4-morpholinopiperidine-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea:

The title compound was prepared following Example 1, substitutingpyridin-3-ylmethanamine and4-(4-morpholinopiperidine-1-ylsulfonyl)aniline for(5-fluoropyridin-3-yl)methanamine and 4-(piperidin-1-ylsulfonyl)aniline,respectively.

¹H NMR (300 MHz, DMSO-d₆): δ 9.17 (s, 1H), 8.51 (d, 1H), 8.44 (dd, 1H),7.68 (dd, 1H), 7.52-7.69 (m, 4H), 7.30-7.38 (m, 1H), 6.89 (t, 1H), 4.32(d, 2H), 3.45-3.59 (m, 6H), 2.30-2.41 (m, 4H), 2.00-2.17 (m, 3H),1.69-1.79 (m, 2H), 1.30-1.44 (m, 2H)

LC-MS: 460.21 (M+1). Example 5

1-[(6-cyanopyridin-3-yl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea

Triphosgene (41 mg, 0.137 mmol) was dissolved in DCM (5 mL) and cooledto −10° C. under N₂ atmosphere. To this cooled solution was addeddropwise a mixture of 4-(piperidin-1-ylsulfonyl) aniline (100 mg, 0.416mmol) and TEA (127 mg, 1.25 mmol) in DCM (5 mL). The mixture was stirredat −10° C. for 5 minutes and allowed to warm up to room temperature for1 hour. A solution of 5-(aminomethyl)picolinonitrile HCl (85 mg, 0.50mmol) and TEA (2.52 mmol) in DCM (5 mL) was then added. The reactionmixture was stirred at room temperature for 16 hours. The mixture wasdiluted with DCM (25 mL), washed with brine (2×15 mL), dried over MgSO₄,filtered and concentrated under reduced pressure. The crude was purifiedby Biotage using 5% MeOH/DCM to afford the desired product as a whiteamorphous powder (54 mg, 32.5% yield).

¹H NMR (300 MHz, DMSO-d₆): δ 8.63 (s, 1H), 7.79 (m, 2H), 7.60 (m, 2H),7.48-7.54 (m, 3H), 6.10 (m, 1H), 4.50 (d, 2H), 2.93 (m, 4H), 1.61 (m,4H), 1.41 (m, 2H)

LC-MS: 400.01 (M+1). Example 6

5-((3-(4-(piperidin-1-yl)phenyl)ureido)methyl)picolinamide

To a solution of1-((6-cyanopyridin-3-yl)methyl)-3-(4-(piperidin-1-ylsulfonyl)phenyl)urea (Example 5, 49 mg, 0.123 mmol) and potassium carbonate (33.9 mg,0.245 mmol) in DMSO (5 mL) was added hydrogen peroxide (0.038 ml, 0.368mmol). The mixture was stirred at room temperature for 16 hours, thenwas diluted with EtOAc and washed successively with 1 M NaOH and brine.The extracts were dried over Na₂SO₄, filtered, concentrated in vacuo,and purified by Biotage using 10% MeOH/DCM to afford the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ 9.00 (s, 1H), 8.42 (m, 2H), 7.62 (dd, 1H),7.52-7.57 (m, 3H), 7.30-7.34 (m, 1H), 6.34 (t, 1H), 3.36-3.39 (m, 2H),2.74-2.82 (m, 4H), 1.51 (m, 4H) 1.32 (m, 2H)

LC-MS: 418.14 (M+1). Example 7

tert-butylN-{5-[({[4-(piperidine-1-sulfonyl)phenyl]carbamoyl}amino)methyl]pyridin-2-yl}carbamate

Triphosgene (122 mg, 0.412 mmol) was dissolved in DCM (5 mL) and cooledto −10° C. under N₂ atmosphere. To this cooled solution was addeddropwise a mixture of 4-(piperidin-1-ylsulfonyl) aniline (300 mg, 1.248mmol) and TEA (2.52 mmol) in DCM (10 mL). The mixture was stirred at−10° C. for 5 minutes and allowed to warm up to room temperature for 1hour. A solution tert-butyl 5-(aminomethyl)pyridin-2-ylcarbamate (293mg, 1.311 mmol) and TEA (2.52 mmol) in DCM (5 mL) was then added. Thereaction mixture was stirred at room temperature for 16 hours. Themixture was diluted with DCM (25 mL), washed with brine (2×15 mL), driedover MgSO₄, filtered and concentrated under reduced pressure. The crudewas purified by Biotage using 5% MeOH/DCM to afford the desired productas a white amorphous powder (200 mg, 32.7% yield).

¹H NMR (300 MHz, DMSO-d₆): δ 8.19 (s, 1H), 7.81 (m, 1H), 7.74 (s, 1H),7.62 (m, 4H), 4.36 (s, 2H), 2.93 (t, 4H), 1.62 (m, 4H), 1.52 (s, 9H),1.42 (m, 2H) LC-MS: 489.99 (M+1).

Example 8

1-((6-aminopyridin-3-yl) methyl-3-(4-(piperidine-1-ylsulfonyl) urea

A solution of tert-butyl 5-((3-(4-(piperidin-1-ylsulfonyl)phenyl)ureido)methyl)-pyridin-2-yl carbamate (Example 7, 87 mg, 0.178mmol) in 20 ml of 1:1 TFA/DCM was stirred at room temperature for 16hours. After removal of the solvent, the residue was purified by Biotageusing 10% MeOH (2 M NH₃)/DCM to afford the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ 8.00 (s, 1H), 7.81 (m, 1H), 7.7.40-7.50 (m,4H), 7.20-7.35 (dd, 1H), 6.38 (d, 1H). 5.77 (t, 1H), 4.18 (d, 2H), 2.85(m, 4H), 1.53 (m, 4H), 1.32 (m, 2H) LC-MS: 390.02 (M+1).

Example 9

4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

A. N-(5-chloro-2-methoxyphenyl)-4-cyanobenzenesulfonamide:

To a solution of 5-chloro-2-methoxyaniline (821 mg, 5.21 mmol, 1.05 eq)and DMAP (61 mg, 0.496 mmol, 0.1 eq) in pyridine (15 mL) cooled to 0° C.was added dropwise a solution of 4-cyanobenzene-1-sulfonyl chloride (1.0g, 4.96 mmol, 1.0 eq) in pyridine (5 mL). The reaction was heated at 80°C. overnight then all volatiles were removed in vacuo. The resultingresidue was dissolved in dichloromethane (20 mL), washed sequentiallywith 1N hydrochloric acid (20 mL), water (20 mL) and saturated sodiumchloride (20 mL) then dried over anhydrous sodium sulfate, filtered andconcentrated under vacuum. The resulting residue was triturated twicewith hexanes (10 mL) and once with diethyl ether (10 mL) and then driedunder vacuum to affordN-(5-chloro-2-methoxyphenyl)-4-cyanobenzenesulfonamide (1.19 g, 74%) asa pale purple solid a portion of which was used without furtherpurification in the subsequent step.

B. 4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)benzoic acid:

N-(5-chloro-2-methoxyphenyl)-4-cyanobenzenesulfonamide (0.387 mmol, 125mg) was dissolved in 2-propanol (8.0 mL) and 1.8 M aqueous potassiumhydroxide (6.5 mL, 11.6 mmol). The reaction was heated at 75° C. for 18hours then cooled to ambient temperature and the 2-propanol removed on arotary evaporator. The aqueous phase was extracted with ethyl acetate (5mL) then the pH was adjusted to pH 2-3 with 2N hydrochloric acid and theaqueous phase was extracted thrice with ethyl acetate (10 mL). Thecombined organic phase was dried over anhydrous sodium sulfate, filteredand concentrated in vacuo to afford4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)benzoic acid as a white solid(123 mg, 93%) which was used without further purification in thesubsequent step.

C.4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide:

To a solution of 4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)benzoic acid(116 mg, 0.340 mmol, 1 eq) in dry DMF (3 mL) was addedimidazo[1,2-a]pyridin-7-ylmethanamine (50 mg, 0.340 mmol, 1 eq),followed by benzotriazol-1-yl-oxytripyrrolidinophosphoniumhexafluorophosphate (PyBOP, 194 mg, 0.374 mmol, 1.1 eq) anddiisopropylethylamine (71 μL, 0.408 mmol, 1.2 eq). The resultant yellowsolution stirred at ambient temperature for 4.5 hrs the all volatileswere removed under vacuum. The crude material was purified by flashcolumn chromatography (eluting with 2-8% methanol/dichloromethane) toafford the title compound as a colorless oil which upon repeatedtrituration with Et₂O gave a white solid (91 mg, 57%).

LCMS MH⁺=471.1 ¹H NMR (DMSO): δH 9.95 (s, 1H), 9.24 (t, 1H), 8.49 (s,1H), 8.00 (2, 2H), 7.94 (s, 1H), 7.82 (d, 2H), 7.53 (m, 2H), 7.19 (m,3H), 6.94 (d, 1H), 4.47 (d, 2H) and 3.48 (s, 3H). Example 10

1-(4-(phenylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

A solution of triphosgene (84 mg, 0.283 mmol) in DCM (5.0 mL) was cooledto −10° C. under N₂ atmosphere and was treated dropwise with a solutionof 4-(phenylsulfonyl)aniline (200 mg, 0.857 mmol) and TEA (260 mg, 2.57mmol) in DCM (5.0 mL). The mixture was stirred at −10° C. for 5 minutes,then at ambient temperature for 1 hour, whereupon this mixture was addedto a solution of pyridin-3-ylmethanamine (97 mg, 0.90 mmol) and TEA (260mg, 2.57 mmol) in DCM (5.0 mL). The mixture was stirred for 16 hours atambient temperature, and then was diluted with DCM (25 mL), washed withbrine (2×15 mL), and dried over MgSO₄. After filtration, the filtratewas concentrated under vacuum and purified by Biotage using 5% MeOH/DCMto afford the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ 4.29 (d, 2H), 6.90 (t, 1H), 7.26-7.35 (m,1H), 7.54-7.70 (m, 6H), 7.65-7.80 (m, 2H), 7.81-7.90 (m, 2H), 8.40-8.45(m, 1H), 8.49-8.55 (m, 1H), 9.21 (s, 1H). LC-MS: 368.15 (M+H).

Example 11

1-(pyridin-3-ylmethyl)-3-(4-(2-(trifluoromethoxy)phenylsulfonyl)phenyl)urea

A: 4-(3-(pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride:

4-Isocyanatobenzene-1-sulfonyl chloride (6 g, 27.6 mmol) was taken up inTHF (250 mL) and cooled to 0° C., whereupon pyridin-3-ylmethanamine(2.79 mL, 27.6 mmol) was added and the resulting mixture was allowed towarm slowly to ambient temperature over 16 hours. The mixture wasfiltered and the filtrate was concentrated to half its original volumeand was treated with 200 mL of anhydrous Et₂O. The precipitates wereagain filtered off and the filtrate was treated with 200 mL of anhydrousEt₂O. The resulting precipitates were collected by vacuum filtration andused in the next step without further purification.

¹H NMR (300 MHz, CDCl₃): δ 4.54 (s, 2H), 7.21 (br s, 1H), 7.33 (d, 2H),7.47 (d, 2H), 8.08 (dd, 1H), 8.55 (dt, 1H), 8.50 (m, 2H), 9.24 (s, 1H).

B: Ammonium 4-(3-(pyridin-3-ylmethyl)ureido)benzenesulfinate:

4-(3-(Pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride (3.99 g,12.25 mmol) was added to a solution of sodium sulfite (6.18 g, 49.0mmol) and sodium bicarbonate (6.17 g, 73.5 mmol) in water (175 mL), andthe resulting mixture was stirred at 80° C. for 3 hours. The mixture wasthen concentrated to dryness under reduced pressure, and the resultingsolids were triturated with hot DMF (100 mL) and the solids filteredoff. The solvent was then removed under reduced pressure, and theresulting residue was triturated with hot DCM (100 mL) and the off-whitecrystalline solids were collected by vacuum filtration. The solids werepurified by SCX ion-exchange column (eluting with 5:1 CH₃CN/NH₄OH) toafford the title compound.

¹H NMR (300 MHz, CDCl₃): δ 4.28 (d, 2H), 7.35 (m, 6H), 7.70 (dt, 1H),8.42 (dd, 1H), 8.51 (d, 1H), 9.23 (br s, 1H). LC-MS: 292.01 (M+1)

C:1-(pyridin-3-ylmethyl)-3-(4-(2-(trifluoromethoxy)phenylsulfonyl)phenyl)urea:

A mixture of ammonium 4-(3-(pyridin-3-ylmethyl)ureido)benzenesulfinate(30.8 mg, 0.1 mmol), 2-(trifluoromethyl)phenylboronic acid (25.7 mg,0.125 mmol), copper(II) acetate (22.7 mg, 0.125 mmol), and TEA (0.063mL, 0.45 mmol) in DMSO (1.5 mL) was heated at 60° C. for 16 hours. Themixture was cooled to ambient temperature and was partitioned betweenEtOAc and brine. The organic layer was separated, dried (MgSO₄),concentrated, and purified by PTLC (100% EtOAc) to afford the titlecompound.

¹H NMR (300 MHz, DMSO-d₆): δ 9.26 (s, 1H), 8.50 (d, 1H), 8.44-8.42 (m,1H), 8.17-8.14 (m, 1H), 7.84-7.78 (m, 1H), 7.75-7.59 (m, 6H), 7.52-7.49(m, 1H), 7.35-7.31 (m, 1H), 6.93 (t, 1H), 4.30 (d, 2H). LC-MS: 452.09(M+1)

Example 12

1-(3-aminobenzvl)-3-(4-(phenylsulfonyl)phenyl)urea

A: tert-butyl3-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)phenylcarbamate:

The title compound was prepared according to Example 1, substitutingtert-butyl 3-(aminomethyl) phenylcarbamate for pyridin-3-ylmethanamine.

¹H NMR (300 MHz, CDCl₃): δ 7.82-7.89 (m, 2H), 7.70-7.76 (m, 2H),7.42-7.58 (m, 4H), 7.38 (d, 2H), 7.29 (s, 1H), 7.10-7.16 (m, 2H),6.62-6.89 (m, 1H), 6.65 (s, 1H), 5.52 (t, 1H), 4.22 (d, 2H), 1.47 (s,9H) LC-MS: 482.08 (M+H).

B: 4-(3-(pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride:

A solution of tert-butyl3-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)phenyl-carbamate (390 mg,0.810 mmol) and TFA (5 mL, 64.9 mmol) in DCM (10 mL) was stirred atambient temperature for 16 hours. The mixture was concentrated andpartitioned between DCM and saturated NaHCO₃. The organic layer waswashed with brine (2×15 mL), dried over Na₂SO₄, filtered, andconcentrated. The residue was purified by Biotage using 10% MeOH/DCM tooffer the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ 9.21 (s, 1H), 8.49-8.55 (m, 2H), 8.40-8.45(m, 2H), 7.81-7.90 (m, 5H), 6.90 (t, 1H), 6.69 (t, 1H), 6.40-6.50 (m,3H), 5.41 (br, s, 2H), 4.14 (d, 2H) LC-MS: 382.28 (M+H).

Example 13

1-(4-(4-chlorophenylthio)phenyl)-3-(pyridin-3-ylmethyl)urea

A: 4-(4-chlorophenylthio)aniline:

A solution of (4-chlorophenyl)(4-nitrophenyl)sulfane (1.71 g, 6.44 mmol)in 2:1 MeOH/EtOAc (75 mL) was treated with platinum(IV) oxide (100 mg)and the resulting mixture was placed under an atmosphere of hydrogen (45psi) for 16 hours. The mixture was filtered through GF/F paper, rinsedwith MeOH, and concentrated under reduced pressure to afford the titlecompound as a yellow solid.

¹H NMR (300 MHz, CDCl₃): δ 7.32-7.27 (m, 2H), 7.19-7.14 (m, 2H),7.05-7.01 (m, 2H), 6.70-6.65 (m, 2H), 3.83 (s, 2H).

B: 1-(4-(4-chlorophenylthio)phenyl)-3-(pyridin-3-ylmethyl)urea:

The title compound was prepared according to Example 1, substituting4-(4-chlorophenylthio)aniline for 4-(phenylsulfonyl)aniline.

¹H NMR (DMSO-d₆): δ 8.90 (s, 1H), 8.51 (d, 1H), 8.45-8.43 (m, 1H),7.71-7.67 (m, 1H), 7.51-7.46 (m, 2H), 7.37-7.31 (m, 5H), 7.11-7.06 (m,2H), 6.81 (t, 1H), 4.30 (d, 2H).

C. 1-(4-(4-chlorophenylthio)phenyl)-3-(pyridin-3-ylmethyl)urea

A solution of1-(4-(4-chlorophenylthio)phenyl)-3-(pyridin-3-ylmethyl)urea (50 mg,0.135 mmol) in 10:1 DCM:MeOH (3.3 mL) was treated with m-CPBA (2.0equiv), and the solution was stirred for 16 hours at ambienttemperature. The mixture was then diluted with saturated NaHCO₃ and DCMand the layers separated. The organic layer was dried over MgSO₄ andpurified by PTLC (6% MeOH/DCM) to afford the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ 9.24 (s, 1H), 8.49 (s, 1H), 8.43-8.42 (m,1H), 7.88 (d, 2H), 7.79 (d, 2H), 7.68-7.58 (m, 5H), 7.35-7.31 (m, 1H),6.92 (t, 1H), 4.30 (d, 2H). LC-MS: 402.00 (M+1)

Example 14

1-((6-(dimethylamino)pyridin-3-yl)methyl)-3-(4-(phenylsulfonyl)phenyl)urea

A: 6-(dimethylamino)nicotinonitrile:

In a sealed tube, 6-chloronicotinonitrile (510 mg, 3.68 mmol) was takenup in DMF (4 mL) and dimethylamine (4.0 mL of a 2.0 M THF solution) andDIEA (3.0 mL, 17.18 mmol) were added. The mixture was heated to 140° C.for 17 hours, and was then diluted with EtOAc and washed with brine (3×)and dried (MgSO₄). After filtration and concentration, the residue waspurified by Biotage SP1 (100% MeOH/DCM/NH₃) to afford the title compoundas a pale yellow solid.

¹H NMR (300 MHz, CDCl₃): δ 8.40 (d, 1H), 7.60-7.56 (m, 1H), 6.49-6.46(m, 1H), 3.15 (s, 6H).

B: 5-(aminomethyl)-N,N-dimethylpyridin-2-amine:

A solution of 6-(dimethylamino)nicotinonitrile (506 mg, 3.44 mmol) in2:1 2N NH₃ (75 mL) was treated with Raney Nickel and placed under a 40psi atmosphere of hydrogen for 16 hours. The mixture was then carefullyfiltered through Celite (caution: to minimize danger of fire, do notallow solids to become dry), the filtrate concentrated to dryness, andpurified by Biotage SP1 (DCM/MeOH/NH₃). The concentrated fractions werethen triturated with Et₂O to afford the title compound as a white solid.

¹H NMR (300 MHz, DMSO-d₆): δ 7.97-7.94 (m, 1H), 7.48-7.37 (m, 1H), 6.57(d, 1H), 3.95 (d, 2H), 3.55 (br s, 2H), 2.96 (s, 6H).

C:1-((6-(dimethylamino)pyridin-3-yl)methyl)-3-(4-(phenylsulfonyl)phenyl)urea

The title compound was prepared according to Example 1, substituting5-(aminomethyl)-N,N-dimethylpyridin-2-amine for pyridin-3-ylmethanamine.

¹H NMR (300 MHz, DMSO-d6): δ 9.05 (s, 1H), 7.99 (d, 1H), 7.90-7.86 (m,2H), 7.77 (d, 2H), 7.65-7.55 (m, 5H), 7.44-7.41 (m, 1H), 6.66 (t, 1H),6.57 (d, 1H), 4.10 (d, 2H), 2.96 (s, 6H). LC-MS: 411.06 (M+1)

Example 15

1-(4-(4-bromophenylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

A: (4-bromophenyl)(4-nitrophenyl)sulfane:

A solution of 4-bromobenzenethiol (4.97 g, 26.3 mmol) in DMF (50 mL) wascooled to 0° C. and treated with K₂CO₃ (4.3 g, 31.1 mmol). Afteraddition was complete, the solution was warmed to ambient temperatureover 15 minutes and then 1-fluoro-4-nitrobenzene (2.62 mL, 24.70 mmol)was added. The mixture was heated to 80° C. for 16 hours, and was thenpoured onto ice and diluted with EtOAc. The layers were separated andthe organic layer was washed successively with saturated NaHCO₃ andbrine (2×). The organics were dried over MgSO₄, filtered, andconcentrated to afford the title compound as a yellow solid.

¹H NMR (300 MHz, DMSO-d₆): δ 8.18-8.13 (m, 2H), 7.87-7.84 (m, 2H),7.53-7.41 (m, 2H), 7.31-7.27 (m, 2H).

B: 4-bromo-2-(4-nitrophenylsulfonyl)benzene:

A solution of (4-bromophenyl)(4-nitrophenyl)sulfane (3.942 g, 12.71mmol) in CHCl₃ (40 ml) was cooled in an ice bath and treated with m-CPBA(2.2 equiv) portionwise. The mixture was allowed to warm slowly toambient temperature over 16 hours, then the mixture was filtered throughGF/F paper and the filtrate washed with 1N NaOH and brine. The organicswere dried over MgSO₄, filtered, and concentrated to the crude solid.The solid can be triturated (if desired) with DCM and collected byvacuum filtration to afford the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ 8.42-8.36 (m, 4H), 8.18-8.13 (m, 2H),7.87-7.84 (m, 2H).

C: 4-(2-bromophenylsulfonyl)aniline:

A mixture of 1-bromo-4-(4-nitrophenylsulfonyl)benzene (1.57 g, 4.59mmol) and tin(II) chloride dihydrate (4.35 g, 22.94 mmol) was heated inEtOH (40 mL) for 2 hours at 70° C. The volatiles were removed underreduced pressure, and the residue was taken up in EtOAc (100 mL) and 2NNaOH (40 mL). The mixture was stirred vigorously for 1 hour, thenfiltered through Celite. The organic layer was separated, dried overMgSO₄, and purified by Biotage SP1 to afford the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ d 7.78-7.71 (m, 4H), 7.52 (d, 2H), 6.59 (d,2H), 6.22 (s, 2H).

D: 1-(4-(4-bromophenylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

The title compound was prepared according to Example 1, substituting4-(4-bromophenylsulfonyl)aniline for 4-(phenylsulfonyl)aniline.

¹H NMR (300 MHz, DMSO-d₆): δ 9.26 (s, 1H), 8.50 (d, 1H), 8.44-8.42 (m,1H), 7.83-7.70 (m, 6H), 7.69-7.65 (m, 1H), 7.62-7.58 (m, 2H), 7.35-7.31(m, 1H), 6.93 (t, 1H), 4.30 (d, 2H). LC-MS: 447.95 (M+1).

Example 16

1-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea

A: tert-butyl5-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)pyridin-2-ylcarbamate:

A solution of 4-phenylsulfonylaniline (1.5 g, 6.43 mmol) in EtOAc (10mL) was added dropwise over 30 minutes to a solution of phosgene (6 ml,20% in Toluene) in toluene (5 mL), and was then heated to reflux for 5hours. The volatiles were removed under reduced pressure, and DCM (50mL), tert-butyl 5-(aminomethyl) pyidin-2-yl carbamate (1.507 g, 6.75mol), and DIEA (4 mL) were added to the residue. The mixture was stirredat ambient temperature for 16 hours, then was diluted with DCM andwashed with saturated sodium bicarbonate. The organics were dried overMgSO₄, concentrated, and purified by Biotage SP1 to afford the titlecompound.

¹H NMR (300 MHz, DMSO-d₆): δ 9.69 (s, 1H), 9.15 (s, 1H), 8.14 (s, 1H),7.87 (dd, 2H), 7.78 (m, 2H), 7.70-7.73 (m, 1H), 7.57-7.66 (m, 6H), 6.81(t, 1H), 4.21 (d, 2H), 1.44 (s, 9H).

B:1-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea:

The title compound was prepared according to Example 3B, substitutingtert-butyl5-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)pyridin-2-ylcarbamate fortert-butyl3-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)phenyl-carbamate.

¹H NMR (300 MHz, CDCl₃): δ 9.03 (s, 1H), 7.86-7.89 (m, 2H), 7.78-7.81(m, 3H), 7.58-7.77 (m, 5H), 7.27-7.31 (dd, 1H), 6.63 (t, 1H), 6.37 (d,1H), 5.81 (s, 2H), 4.06 (d, 2H)

LC-MS: 383.13 (M+1).

Example 17

1-(4-(phenylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

A mixture of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine)(37.8 mg, 0.065 mmol), Cs₂CO₃ (319 mg, 0.980 mmol),tri(dibenzylideneacetone)dipalladium(0) (29.9 mg, 0.033 mmol), sodium4-methylbenzenesulfinate (140 mg, 0.784 mmol),1-(4-bromophenyl)-3-(pyridine-3-ylmethyl)urea (200 mg, 0.653 mg), andtetrabutylammonium iodide (290 mg, 0.784 mmol) in toluene (10 mL) washeated at 100° C. for 16 hours. The mixture was cooled to ambienttemperature and DCM was added. The organic layer was washed successivelywith water and brine, dried over MgSO₄, concentrated, and purified byBiotage SP1 to afford the title compound.

¹H NMR (300 MHz, CDCl₃): δ 8.47 (s, 1H), 8.44 (d, 1H), 8.32 (s, 1H),7.69-7.74 (m, 4H), 7.63 (d, 1H), 7.47-7.51 (dd, 2H), 7.26-7.46 (m, 3H),6.12 (s, 1H), 4.38 (d, 2H), 2.37 (s, 3H) LC-MS: 382.15 (M+1).

Example 18

N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(phenylsulfonyl)benzamide

A. 4-sulfonylbenzonitrile:

4-fluorobenzonitrile (46.5 mmol, 5.63 g) and sodium benzenesulfinate(51.1 mmol, 8.39 g) were dissolved in DMSO (35.8 mL). The reaction washeated at 130° C. for 48 hours then cooled to ambient temperature andpoured onto ice. The precipitated solids were collected by suctionfiltration, washed with water and then dried under vacuum to afford4-sulfonylbenzonitrile (11.2 g) a portion of which was used in thesubsequent step without further purification.B. 4-phenylsulfonylbenzoic acid:

4-sulfonylbenzonitrile (4.11 mmol, 1.0 g) was dissolved in 2-propanol(88 mL) and 1.0 M aqueous potassium hydroxide (140 mL). The reaction washeated at 75° C. for 18 hours then cooled to ambient temperature and the2-propanol removed on a rotary evaporator. The aqueous phase wasextracted with ethyl acetate (70 mL) then the pH was adjusted to pH 2-3with 6N hydrochloric acid and the aqueous phase was extracted thricewith ethyl acetate (100 mL). The combined organic phase was dried overanhydrous magnesium sulfate, filtered and concentrated in vacuo toafford 4-phenylsulfonylbenzoic acid as a white solid (1.01 g) a portionof which was used without further purification in the subsequent step.C. N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(phenylsulfonyl)benzamide:

Oxalyl chloride (66.7 μL, 0.763 mmol) was added dropwise to a solutionof 4-phenylsulfonylbenzoic acid (100 mg, 0.381 mmol) in dichloromethane(3.81 mL) at 0° C. The reaction stirred for 2 hours then all volatileswere removed under vacuum. The crude 4-phenylsulfonylbenzoyl chloridewas re-dissolved in dichloromethane (3.8 mL) thenimidazo[1,2-a]pyridin-7-ylmethanamine hydrochloride (77 mg, 0.419 mmol)and triethylamine (117 μL, 0.839 mmol) were added successively. Thereaction stirred for 1 hour at ambient temperature then saturated sodiumbicarbonate (3.8 mL) was added. The organic phase was separated, washedwith saturated sodium chloride (3 mL), dried over anhydrous magnesiumsulfate and concentrated in vacuum. The resulting residue was purifiedby flash column chromatography (eluting with 5% methanol/dichlormethane)to afford the title compound as a white solid (73 mg, 49%).

LCMS MH⁺=391.9 ¹H NMR (MeOD): δH 8.29 (s, 1H), 8.00 (s, 4H), 7.93 (d,2H), 7.65-7.48 (m, 6H), 7.27 (dd, 1H) and 4.50 (s, 2H). Assays: AssayExample 1 Biochemical Inhibition Assay NAMPT Protein Purification

Recombinant His-tagged NAMPT was produced in E. coli cells, purifiedover a Ni column, and further purified over a size-exclusion column byXTAL Biostructures.

The NAMPT Enzymatic Reaction

The NAMPT enzymatic reactions were carried out in Buffer A (50 mM HepespH 7.5, 50 mM NaCl, 5 mM MgCl₂, and 1 mM THP) in 96-well V-bottomplates. The compound titrations were performed in a separate dilutionplate by serially diluting the compounds in DMSO to make a 100× stock.Buffer A (89 μL) containing 33 nM of NAMPT protein was added to 1 μL of100× compound plate containing controls (e.g. DMSO or blank). Thecompound and enzyme mix was incubated for 15 minutes at roomtemperature, then 10 μL of 100× substrate and co-factors in Buffer Awere added to the test well to make a final concentration of 1 μM NAM,100 μM 5-Phospho-D-ribose 1-diphosphate (PRPP), and 2.5 mM Adenosine5′-triphosphate (ATP). The reaction was allowed to proceed for 30minutes at room temperature, then was quenched with the addition of 11μL of a solution of formic acid and L-Cystathionine to make a finalconcentration of 1% formic acid and 10 μM L-Cystathionine. Backgroundand signal strength was determined by addition (or non-addition) of aserial dilution of NMN to a pre-quenched enzyme and cofactor mix.

Quantification of NMN

A mass spectrometry-based assay was used to measure the NAMPT reactionproduct (NMN) and the internal control (L-Cystathionine). NMN andL-Cystathionine were detected using the services of Biocius Lifescienceswith the RapidFire system. In short, the NMN and L-Cystathionine arebound to a graphitic carbon cartridge in 0.1% formic acid, eluted in 30%acetonitrile buffer, and injected into a Sciex 4000 mass spectrometer.The components of the sample were ionized with electrospray ionizationand the positive ions were detected. The Q1 (parent ion) and Q3(fragment ion) masses of NMN were 334.2 and 123.2, respectively. The Q1and Q3 for L-Cystathionine were 223.1 and 134.1, respectively. Thefragments are quantified and the analyzed by the following method.

% inhibitions are determined using this method.

First the NMN signal is normalized to the L-Cystathionine signal bydividing the NMN signal by the L-Cystathionine signal for each well. Thesignal from the background wells are averaged and subtracted from thetest plates. The compound treated cells re then assayed for % inhibitionby using this formula.

% Inh=100−100*x/y

wherein x denotes the average signal of the compound treated wells and ydenotes the average signal of the DMSO treated wells.IC50s are determined using Excel and this formula.

IC50=10{circumflex over ( )}(LOG 10(X)+(((50-% Inh at CmpdConcentration1)/(XX-YY)*(LOG 10(X)-LOG 10(Y))))

wherein X denotes the compound concentration 1, Y denotes the compoundconcentration 2, XX denotes the % inhibition at compound concentration 1(X), and YY denotes the % inhibition at compound concentration 2 (Y).

The NAMPT-inhibitor compounds of this invention have IC50 values thatare under 10 μM, preferably under 1 μM, more preferably under 0.1 μM,and most preferably under 0.01 μM. Results for representative compoundsare provided in Table 3 below.

Assay Example 2 In-Vitro Cell Proliferation Assay

A2780 cells were seeded in 96-well plates at 1×10³ cells/well in 180 μLof culture medium (10% FBS, 1% Pen/Strep Amphotecricin B, RPMI-1640)with and without the addition of either 3-nicotinamide mononucleotide(NMN) or nicotinamide (NAM). After overnight incubation at 37° C. and 5%CO₂, the compound titrations were performed in a separate dilution plateby serially diluting the compounds in DMSO to make a 1000× stock. Thecompounds were then further diluted to 10× final concentration inculture media, whereupon 20 μL of each dilution was added to the platedcells with controls (e.g. DMSO and blank) to make a final volume of 200μL. The final DMSO concentration in each well was 0.1%. The plates werethen incubated for 72 hours at 37° C. in a 5% CO₂ incubator. The numberof viable cells was then assessed using sulforhodamine B(SRB) assay.Cells were fixed at 4° C. for 1 hour with the addition of 50 μL 30%trichloroacetic acid (TCA) to make a final concentration of 6% TCA. Theplates were washed four times with H₂O and allowed to dry for at least 1hour, whereupon 100 μL of a 4% SRB in 1% acetic acid solution was addedto each well and incubated at room temperature for at least 30 minutes.The plates were then washed three times with 1% acetic acid, dried, andtreated with 100 μL of 10 mM Tris-Base solution. The plates were thenread in a microplate reader at an absorbance of 570 nm. Background wasgenerated on a separate plate with media only.

Method for Determining % Inhibition

First, the signals from the background plate are averaged, then thebackground was subtracted from the test plates. The compound-treatedcells were then assayed for % inhibition by using the following formula:

% Inh=100−100*x/y

wherein x denotes the average signal of the compound-treated cells and ydenotes the average signal of the DMSO-treated cells.

Formula for Determining IC₅₀ Values:

IC50=10{circumflex over ( )}(LOG 10(X)+(((50-% Inh at CmpdConcentration1)/(XX-YY)*(LOG 10(X)-LOG 10(Y))))

wherein X denotes the compound concentration 1, Y denotes the compoundconcentration 2, XX denotes the % inhibition at compound concentration 1(X), and YY denotes the % inhibition at compound concentration 2 (Y).

Specificity of Cytotoxicity.

Inhibition of NAMPT could be reversed by the addition of NAM or NMN. Thespecificity of the compounds were determined via cell viability assay inthe presence of the compound and either NAM or NMN. Percent inhibitionswere determined using the method given above.

The NAMPT-inhibitor compounds of this invention have IC50 values thatare preferably under 1 μM, more preferably under 0.1 μM, and mostpreferably under 0.01 μM. Most preferable compounds of this inventionare compounds that have both the enzymatic IC50-value and the A2780IC50-value under 10 μM, preferably under 1 μM, more preferably under 0.1μM, and most preferably under 0.01 μM.

Results for representative compounds is provided in Table 3 below.

TABLE 3 Biochem A2780 Compound IC50 uM IC50 uM(3S)-N,N-diethyl-1-[(4-{[(pyridin-3- 0.006 0.025ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-3-carboxamide1-(4-{[(1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl]sulfamoyl}phenyl)-3-(pyridin-0.007 0.046 3-ylmethyl)urea1-(4-{[2-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.0050.011 ylmethyl)urea1-(4-{[2-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.0040.018 ylmethyl)urea1-(4-{[3-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.0060.103 ylmethyl)urea1-(4-{[4-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.0050.173 ylmethyl)urea1-(4-{[4-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.0040.054 ylmethyl)urea 1-(4-{2-azabicyclo[2.2.1]heptane-2-sulfonyl}phenyl)-0.01 0.236 3-(pyridin-3-ylmethyl)urea1-(4-{2-oxa-8-azaspiro[4.5]decane-8-sulfonyl}phenyl)- 0.005 0.0893-(pyridin-3-ylmethyl)urea1-(4-{3-[(2-oxopyrrolidin-1-yl)methyl]piperidine-1-sulfonyl}phenyl)-3-0.003 0.143 (pyridin-3-ylmethyl)urea1-(4-{3-azaspiro[5.5]undecane-3-sulfonyl}phenyl)- 0.011 0.1453-(pyridin-3-ylmethyl)urea1-(4-{3-azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11- 0.002 0.026pentaene-3-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea1-(4-{3-oxa-8-azabicyclo[3.2.1]octane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea0.012 0.2871-(4-{4-[(2-oxopyrrolidin-1-yl)methyl]piperidine-1-sulfonyl}phenyl)-3-0.002 0.078 (pyridin-3-ylmethyl)urea1-(4-{4-[(furan-2-yl)carbonyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-0.004 0.168 ylmethyl)urea1-(4-{4-[2-(morpholin-4-yl)-2-oxoethyl]piperazine-1-sulfonyl}phenyl)-3-0.004 0.135 (pyridin-3-ylmethyl)urea1-(4-{4-[2-oxo-2-(piperidin-1-yl)ethyl]piperazine-1-sulfonyl}phenyl)-3-0.009 0.021 (pyridin-3-ylmethyl)urea1-(4-{4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]piperazine-1-sulfonyl}phenyl)-3-0.004 0.099 (pyridin-3-ylmethyl)urea1-(4-{4-[3-(morpholin-4-yl)propyl]piperazine-1-sulfonyl}phenyl)-3- 0.0030.024 (pyridin-3-ylmethyl)urea1-(4-{8-azabicyclo[3.2.1]octane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea0.004 0.0641-(4-{8-azaspiro[4.5]decane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea0.004 0.3431-(4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea0.007 0.029 1-(pyridin-3-ylmethyl)-3-(4-{[(1R,2R,3R,5S)-2,6,6- 0.080.091 trimethylbicyclo[3.1.1]heptan-3-yl]sulfamoyl}phenyl)urea1-(pyridin-3-ylmethyl)-3-(4-{[2- 0.0012 0.007(trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea1-(pyridin-3-ylmethyl)-3-(4-{[3- 0.006(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea1-(pyridin-3-ylmethyl)-3-[4-(1H-pyrrole-1-sulfonyl)phenyl]urea 0.0191.788 1-(pyridin-3-ylmethyl)-3-{4-[(3S)-3-(trifluoromethyl)piperidine-1-0.003 0.029 sulfonyl]phenyl}urea1-(pyridin-3-ylmethyl)-3-{4-[3-(trifluoromethyl)piperidine-1- 0.0030.026 sulfonyl]phenyl}urea 1-[(3,4-difluorophenyl)methyl]-3-[4- 0.092 29(piperidine-1-sulfonyl)phenyl]urea1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-4-carboxamide0.01 1.4811-[(4-fluorophenyl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea 0.245251-[(6-isocyanopyridin-3-yl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea1.734 >301-[3-(piperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea >30 >301-[4-(2,6-dimethylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.011 0.1641-[4-(3,4-dihydro-2H-1,4-benzoxazine-4-sulfonyl)phenyl]-3-(pyridin-3-0.01 0.459 ylmethyl)urea1-[4-(3,5-dimethylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3- 0.0060.014 ylmethyl)urea1-[4-(4,4-difluoropiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.025 0.2991-[4-(4-{[(2R)-oxolan-2-yl]carbonyl[piperazine-1-sulfonyl)phenyl]-3-0.008 0.030 (pyridin-3-ylmethyl)urea1-[4-(4-benzyl-1,4-diazepane-1-sulfonyl)phenyl]-3-(pyridin-3- 0.0050.137 ylmethyl)urea1-[4-(4-phenylpiperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.0051-[4-(4-phenylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.003 1-[4-(cycloheptylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.003 0.080 1-[4-(cyclohexylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.001 0.2041-[4-(decahydroquinoline-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.011 0.014 1-[4-(dibenzylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.0008 0.00031-[4-(morpholine-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.0231.35 1-[4-(piperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.011 0.1671-{4-[(1-phenylcyclopentyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea0.029 0.180 1-{4-[(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine]-1′-0.005 0.041 ylsulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea1-{4-[(2-phenylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.0030.0471-{4-[(2R)-2-(morpholin-4-ylmethyl)piperidine-1-sulfonyl]phenyl}-3-0.051 0.081 (pyridin-3-ylmethyl)urea1-{4-[(2R)-2-benzylpiperidine-1-sulfonyl]phenyl}-3-(pyridin-3- 0.0040.024 ylmethyl)urea1-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-3- 0.008 0.025{imidazo[1,2-a]pyridin-6-ylmethyl}urea1-{4-[(cyclohexylmethyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea0.004 0.1811-{4-[(naphthalen-1-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea0.001 0.0191-{4-[4-(2-oxo-2,3-dihydro-1H-indol-1-yl)piperidine-1-sulfonyl]phenyl}-3-0.003 0.058 (pyridin-3-ylmethyl)urea1-{4-[4-(azepan-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3- 0.0050.006 ylmethyl)urea1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-0.009 0.013 ylmethyl)urea1-{4-[4-(piperidin-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-0.007 0.013 ylmethyl)urea 2-methyl-N-{1-[(4-{[(pyridin-3- 0.005 0.123ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidin-4-yl}propanamide3-(4-{[(2-chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.0030.201 ylmethyl)urea3-(4-{[(2-methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.0080.097 ylmethyl)urea3-(4-{[(3-fluorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-0.002 0.156 ylmethyl)urea3-(4-{[(4-chlorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-0.002 0.484 ylmethyl)urea3-(4-{[(4-fluorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-0.003 ylmethyl)urea3-(4-{[(4-methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.0160.507 ylmethyl)urea3-(4-{[(5-ethylpyridin-2-yl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-0.005 0.134 3-ylmethyl)urea3-(4-{[2-(4-fluorophenoxy)pyridin-3-yl]sulfamoyl}phenyl)-1-(pyridin-3-0.011 0.149 ylmethyl)urea 3-(4-{[2-(difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.0006 0.031 ylmethyl)urea3-(4-{[2-(morpholin-4-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-0.008 0.007 (pyridin-3-ylmethyl)urea3-(4-{[2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-0.005 0.022 (pyridin-3-ylmethyl)urea3-(4-{[2-(propan-2-yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.0020.015 ylmethyl)urea3-(4-{[2-methoxy-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-0.0001 0.002 3-ylmethyl)urea3-(4-{[3-chloro-4-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-0.001 0.024 ylmethyl)urea3-(4-{[3-methyl-4-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-0.002 0.108 ylmethyl)urea3-(4-{[4-chloro-2-(trifluoromethoxy)phenyl]sulfamoyl[phenyl)-1-(pyridin-0.006 0.113 3-ylmethyl)urea3-(4-{[4-methyl-3-(trifluoromethyl)phenyl]sulfamoyl[phenyl)-1-(pyridin-0.002 0.179 3-ylmethyl)urea3-(4-{4-[(4-fluorophenyl)carbonyl]piperidine-1-sulfonyl}phenyl)-1- 0.0100.206 (pyridin-3-ylmethyl)urea3-(4-{4-[(morpholin-4-yl)carbonyl]piperidine-1-sulfonyl}phenyl)-1- 0.0080.04 (pyridin-3-ylmethyl)urea3-(4-{4-[1-(3-methoxyphenyl)-4-methylcyclohexyl]piperazine-1- 0.0040.005 sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea3-(4-{4-[2-(diethylamino)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-0.004 0.023 ylmethyl)urea3-(4-{4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazine-1- 0.0050.128 sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea3-(4-{4-[bis(4-fluorophenyl)methyl]piperazine-1-sulfonyl}phenyl)-1-0.005 0.007 (pyridin-3-ylmethyl)urea3-(4-{8-methyl-2,8-diazaspiro[5.5]undecane-2-sulfonyl}phenyl)-1- 0.0010.001 (pyridin-3-ylmethyl)urea3-(4-{methyl[(1S)-1-phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.0010.008 ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-(4-{[(1S,2S,3S,5R)-2,6,6-0.012 0.096 trimethylbicyclo[3.1.1]heptan-3-yl]sulfamoyl}phenyl)urea3-(pyridin-3-ylmethyl)-1-(4-{[2-(1H-pyrrol-1- 0.003 0.076yl)phenyl]sulfamoyl}phenyl)urea3-(pyridin-3-ylmethyl)-1-(4-{[2-(pyrrolidin-1- 0.013 0.011yl)phenyl]sulfamoyl}phenyl)urea3-(pyridin-3-ylmethyl)-1-[4-(5,6,7,8-tetrahydro-1,6-naphthyridine-6-0.016 0.111 sulfonyl)phenyl]urea3-(pyridin-3-ylmethyl)-1-[4-(pyrrolidine-1-sulfonyl)phenyl]urea 0.0371.3993-(pyridin-3-ylmethyl)-1-{4-[(3S)-3-[(pyrrolidin-1-yl)carbonyl]piperidine-0.009 0.137 1-sulfonyl]phenyl}urea3-(pyridin-3-ylmethyl)-1-{4-[(5,6,7,8-tetrahydronaphthalen-1- 0.00030.045 yl)sulfamoyl]phenyl}urea3-[(2-fluorophenyl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea0.016 >303-[(3-fluorophenyl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea0.033 >303-[(5-chloropyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea0.048 183-[(6-chloropyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea0.008 >303-[2-fluoro-4-(piperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.023 1.0053-[4-({[4-(dimethylamino)phenyl]methyl}sulfamoyl)phenyl]-1-(pyridin-3-0.003 0.148 ylmethyl)urea3-[4-({2-[(2S)-2-hydroxypropoxy]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-0.012 0.088 ylmethyl)urea3-[4-({3-[(1S)-1-hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-0.007 0.164 ylmethyl)urea3-[4-(2,3-dihydro-1H-indole-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.002 0.0313-[4-(3,3-difluoroazetidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.059 7.8593-[4-(3-methylpiperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.007 0.0673-[4-(4-methylpiperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.004 0.254 3-[4-(azepane-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.007 0.1393-[4-(azetidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0411.622 3-[4-(diethylsulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0163-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrazin-2-ylmethyl)urea 0.273 >303-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrimidin-5-ylmethyl)urea1.14 >303-[4-(piperidine-1-sulfonyl)phenyl]-1-[1-(pyridin-3-yl)ethyl]urea22.089 >303-[4-(piperidine-1-sulfonyl)phenyl]-1-[2-(pyridin-3-yl)ethyl]urea 0.010.6613-[4-(piperidine-1-sulfonyl)phenyl]-1-{[6-(trifluoromethyl)pyridin-3-0.189 >30 yl]methyl]urea3-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1-(pyridin-3-yl)urea 0.0372.2593-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1-(pyridin-3-ylmethyl)urea0.017 0.5473-{4-[(2,2-dimethylpropyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.017 0.1593-{4-[(2,3-dichlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.002 0.0303-{4-[(2,3-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0009 0.0743-{4-[(2,4-dichlorophenyl)sulfamoyl]phenyl]-1-(pyridin-3-ylmethyl)urea0.003 0.1893-{4-[(2,4-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.003 0.1093-{4-[(2,5-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0012 0.0043-{4-[(2,5-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.006 0.1163-{4-[(2-bromophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0020.024 3-{4-[(2-chloro-4-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-0.0009 0.036 ylmethyl)urea3-{4-[(2-chloro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0010.032 ylmethyl)urea3-{4-[(2-chloro-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.00030.009 ylmethyl)urea3-{4-[(2-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0030.041 3-{4-[(2-ethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.003 0.0323-{4-[(2-fluoro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0020.157 ylmethyl)urea3-{4-[(2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0083-{4-[(2-iodophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.00080.039 3-{4-[(2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-0.002 0.002 ylmethyl)urea3-{4-[(2-methoxypyridin-3-yl)sulfamoyl]phenyl}-1-(pyridin-3- 0.007 0.114ylmethyl)urea3-{4-[(2-phenylpropan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.005 0.0393-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-1-(pyridin-3-0.01 0.009 ylmethyl)urea3-{4-[(2S)-2-(methoxymethyl)pyrrolidine-1-sulfonyl]phenyl}-1-(pyridin-3-0.002 0.060 ylmethyl)urea3-{4-[(2S)-2-ethylpiperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.0040.018 ylmethyl)urea3-{4-[(3,4-dichlorophenyl)sulfamoyl]phenyl]-1-(pyridin-3-ylmethyl)urea0.006 0.1223-{4-[(3,4-dimethoxyphenyl)sulfamoyl]phenyl]-1-(pyridin-3-ylmethyl)urea0.005 0.1163-{4-[(3,4-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.003 0.0933-{4-[(3,5-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.005 0.0963-{4-[(3,5-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.001 0.0413-{4-[(3-aminophenyl)(methanesulfonyl)sulfamoyl]phenyl}-1-(pyridin-3-0.003 0.110 ylmethyl)urea3-{4-[(3-bromophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0033-{4-[(3-chloro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.00140.026 ylmethyl)urea3-{4-[(3-chlorophenyl)sulfamoyl]phenyl]-1-(pyridin-3-ylmethyl)urea 0.0013-{4-[(3-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0020.057 ylmethyl)urea3-{4-[(3-methoxy-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0040.148 ylmethyl)urea3-{4-[(3-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0103-{4-[(3S)-3-methyl-4-(3-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-0.003 0.034 (pyridin-3-ylmethyl)urea3-{4-[(3S)-3-methyl-4-(4-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-0.004 0.095 (pyridin-3-ylmethyl)urea3-{4-[(3S)-3-methylpiperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.0030.105 ylmethyl)urea3-{4-[(4-chloro-2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-0.001 0.006 3-ylmethyl)urea3-{4-[(4-chloronaphthalen-1-yl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0050.053 ylmethyl)urea3-{4-[(4-ethoxy-2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0040.157 ylmethyl)urea3-{4-[(4-ethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0073-{4-[(4-fluoro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0070.116 ylmethyl)urea3-{4-[(4-tert-butyl-2-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-0.0014 0.097 ylmethyl)urea3-{4-[(5-chloro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.00090.003 ylmethyl)urea3-{4-[(5-chloro-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0010.035 ylmethyl)urea3-{4-[(5-fluoro-2-methoxyphenyl)sulfamoyl]phenyl]-1-(pyridin-3- 0.00100.033 ylmethyl)urea3-{4-[(5-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0020.079 ylmethyl)urea3-{4-[3-(2-methoxyethyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-0.004 0.089 ylmethyl)urea3-{4-[4-(2,5-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-0.005 0.101 ylmethyl)urea3-{4-[4-(2-ethoxyphenyl)piperazine-1-sulfonyl]phenyl]-1-(pyridin-3-0.002 0.006 ylmethyl)urea3-{4-[4-(2-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-0.007 0.035 ylmethyl)urea3-{4-[4-(2-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-0.006 0.106 ylmethyl)urea3-{4-[4-(3,5-dichloropyridin-4-yl)piperazine-1-sulfonyl]phenyl}-1- 0.0030.029 (pyridin-3-ylmethyl)urea3-{4-[4-(3-chloropyridin-2-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-0.001 0.018 ylmethyl)urea3-{4-[4-(5-chloro-2-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1- 0.0020.050 (pyridin-3-ylmethyl)urea3-{4-[4-(5-chloro-2-methylphenyl)piperazine-1-sulfonyl]phenyl}-1- 0.0020.162 (pyridin-3-ylmethyl)urea3-{4-[4-(diethylamino)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.0050.014 ylmethyl)urea3-{4-[4-(dipropylamino)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.0040.003 ylmethyl)urea3-{4-[4-(methoxymethyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.0220.130 ylmethyl)urea3-{4-[benzyl(ethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.00090.007 3-{4-[benzyl(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0011 0.1073-{4-[benzyl(propan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.002 0.0263-{4-[cyclohexyl(ethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.005 0.1233-{4-[methyl({[3-(trifluoromethyl)phenyl]methyl})sulfamoyl]phenyl}-1-0.007 (pyridin-3-ylmethyl)urea3-{4-[methyl(2-methylpropyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.007ylmethyl)urea 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4-{8-oxa-3- 0.0080.006 azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)urea3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-{4-[4-(morpholin-4-yl)piperidine-0.004 0.005 1-sulfonyl]phenyl}urea3-benzyl-1-[4-(piperidine-1-sulfonyl)phenyl]urea 0.718 >305-[({[4-(piperidine-1-sulfonyl)phenyl]carbamoyl}amino)methyl]pyridine- >1027.477 2-carboxamide N-(propan-2-yl)-2-{4-[(4-{[(pyridin-3- 0.003 0.037ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamideN,N-diethyl-2-[(4-{[(pyridin-3- 0.008 0.006ylmethyl)carbamoyl]amino]benzene)sulfonamido]benzamideN,N-diethyl-2-{4-[(4-{[(pyridin-3- 0.005 0.045ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamideN,N-dimethyl-1-[(4-{[(pyridin-3- 0.009 0.164ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-4-carboxamideN,N-dimethyl-2-[(4-{[(pyridin-3- 0.016 0.055ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamideN-ethyl-N-[(3S)-1-[(4-{[(pyridin-3- 0.006 0.079ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidin-3-yl]acetamideN-methyl-2-[(4-{[(pyridin-3- 0.001 0.011ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamideN-methyl-N-phenyl-2-{4-[(4-{[(pyridin-3- 0.008 0.030ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamiderel-3-{4-[(4aR,8aS)-decahydroisoquinoline-2-sulfonyl]phenyl}-1-(pyridin-0.002 0.101 3-ylmethyl)urea tert-butylN-{5-[({[4-(piperidine-1- 3.1359.782 sulfonyl)phenyl]carbamoyl}amino)methyl]pyridin-2-yl}carbamate1-(4-{8-oxatricyclo[7.4.0.0²,⁷]trideca-1(9),2(7),3,5,10,12-hexaene-6-0.002 0.003 sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea1-(4-benzoylphenyl)-3-(pyridin-3-ylmethyl)urea 0.017 0.7351-(pyridin-3-ylmethyl)-3-(4-{[2- 0.001 0.003(trifluoromethoxy)benzene]sulfonyl}phenyl)urea1-(pyridin-3-ylmethyl)-3-(4-{[2- 0.003 0.569(trifluoromethyl)benzene]sulfonyl}phenyl)urea1-(pyridin-3-ylmethyl)-3-(4-{[3- 0.001 0.083(trifluoromethoxy)benzene]sulfonyl}phenyl)urea1-(pyridin-3-ylmethyl)-3-(4-{[3- 0.004 0.247(trifluoromethyl)benzene]sulfonyl}phenyl)urea1-(pyridin-3-ylmethyl)-3-(4-{[4- 0.005 0.420(trifluoromethoxy)benzene]sulfonyl}phenyl)urea1-(pyridin-3-ylmethyl)-3-(4-{[4- 0.009 0.604(trifluoromethyl)benzene]sulfonyl}phenyl)urea1-(pyridin-3-ylmethyl)-3-[4-(trifluoromethane)sulfonylphenyl]urea 0.22610.01-(pyridin-3-ylmethyl)-3-{4-[(2,4,6-trimethylbenzene)sulfonyl]phenyl}urea0.011 >11-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea 0.0030.081 1-[(6-aminopyridin-3-yl)methyl]-3-{4-[(4- 0.002 0.043fluorobenzene)sulfonyl]phenyl}urea1-[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.001 0.3221-[4-(benzenesulfonyl)phenyl]-3-(1H-pyrazol-3-ylmethyl)urea >10 >201-[4-(benzenesulfonyl)phenyl]-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea0.001 0.0331-[4-(benzenesulfonyl)phenyl]-3-{thieno[2,3-c]pyridin-2-ylmethyl}urea0.46 >30 1-[4-(cyclopentanesulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.043 1.861-[6-(benzenesulfonyl)pyridin-3-yl]-3-(pyridin-3-ylmethyl)urea 0.0152.356 1-{[4-(benzenesulfonyl)phenyl]methyl}-3-(quinolin-6-yl)urea2.258 >301-{4-[(2-phenoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea0.002 0.0081-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-0.003 0.029 ylmethyl[urea3-(4-{[2-(methoxymethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.0060.039 ylmethyl)urea3-(4-{[2-chloro-5-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.005 0.339 ylmethyl)urea3-(4-{[2-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.001 0.014 ylmethyl)urea3-(4-{[2-methoxy-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1- 0.0020.003 (pyridin-3-ylmethyl)urea3-(4-{[2-methoxy-5-(propan-2-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.003 0.031 ylmethyl)urea3-(4-{[2-methyl-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-0.002 0.021 3-ylmethyl)urea3-(4-{[3-(propan-2-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.002 0.038ylmethyl)urea3-(4-{[3-(propan-2-yloxy)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.0040.079 ylmethyl)urea3-(4-{[3-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.000 0.054 ylmethyl)urea3-(4-{[4-chloro-3-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.005 0.167 ylmethyl)urea3-(pyridin-3-ylmethyl)-1-[4-(pyridine-2-sulfonyl)phenyl]urea 0.8693-(pyridin-3-ylmethyl)-1-[4-(pyridine-3-sulfonyl)phenyl]urea 0.005 0.5953-(pyridin-3-ylmethyl)-1-[4-(pyridine-4-sulfonyl)phenyl]urea 0.011 0.4883-(pyridin-3-ylmethyl)-1-[4-(pyrimidine-5-sulfonyl)phenyl]urea 0.0200.8713-[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.004 0.247 3-[4-(2-methoxynaphthalene-1-sulfonyl)phenyl]-1-(pyridin-3-0.002 0.012 ylmethyl)urea3-[4-(3,5-dimethyl-1,2-oxazole-4-sulfonyl)phenyl]-1-(pyridin-3- 0.0200.850 ylmethyl)urea3-[4-(5-methylthiophene-2-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.003 0.383 3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3-yl)urea >3027.465 3-[4-(benzenesulfonyl)phenyl]-1-(quinolin-6-yl)urea 0.090 15.863-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-imidazol-1-yl)pyridin-3- >10yl]methyl}urea3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-pyrazol-1-yl)pyridin-3-3.791 >10 yl]methyl}urea3-[4-(benzenesulfonyl)phenyl]-1-{[6-(2-methoxyethoxy)pyridin-3-2.121 >10 yl]methyl}urea 3-{[({4-[(4- 0.444 20.611chlorobenzene)sulfinyl]phenyl}carbamoyl)amino]methyl}pyridin-1-ium-1-olate 3-{[({4-[(4- 0.728 >30chlorobenzene)sulfonyl]phenyl}carbamoyl)amino]methyl}pyridin-1-ium-1-olate3-{4-[(2,3-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.001 0.4463-{4-[(2,3-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.004 0.5463-{4-[(2,3-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.005 0.2983-{4-[(2,4-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.004 0.8273-{4-[(2,4-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.001 0.3443-{4-[(2,4-dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.005 0.0473-{4-[(2,4-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.018 0.9673-{4-[(2,5-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.006 0.6523-{4-[(2,5-difluoro-4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-0.004 0.105 ylmethyl)urea3-{4-[(2,5-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.004 0.4033-{4-[(2,5-dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.001 0.0073-{4-[(2,5-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.014 0.4733-{4-[(2,6-dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.007 0.0263-{4-[(2,6-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.008 0.3873-{4-[(2-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0020.326 3-{4-[(2-bromobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.006 0.2503-{4-[(2-chloro-4-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.008ylmethyl)urea3-{4-[(2-chloro-6-fluoro-3-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-0.007 0.336 ylmethyl)urea3-{4-[(2-chlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0050.475 3-{4-[(2-ethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.002 0.00043-{4-[(2-ethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0020.169 3-{4-[(2-fluoro-3-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-0.001 0.387 ylmethyl)urea3-{4-[(2-fluoro-4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0030.311 ylmethyl)urea3-{4-[(2-fluoro-4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0020.517 ylmethyl)urea3-{4-[(2-fluoro-5-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.012 >1ylmethyl)urea3-{4-[(2-fluoro-6-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0020.010 ylmethyl)urea3-{4-[(2-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0030.493 3-{4-[(2-methoxy-5-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-0.004 0.007 ylmethyl)urea3-{4-[(2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.002 0.0103-{4-[(2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0020.4503-{4-[(3,4-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.003 0.2143-{4-[(3,4-dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.005 0.0173-{4-[(3,5-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.003 0.2843-{4-[(3,5-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.001 0.0403-{4-[(3-bromobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0020.322 3-{4-[(3-chlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.003 0.5183-{4-[(3-fluoro-4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0020.173 ylmethyl)urea3-{4-[(3-fluoro-4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0010.206 ylmethyl)urea3-{4-[(3-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0010.238 3-{4-[(3-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.002 0.1573-{4-[(4-chloro-2-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0020.415 ylmethyl)urea3-{4-[(4-chloro-2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0060.755 ylmethyl)urea3-{4-[(4-chloro-3-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0030.221 ylmethyl)urea3-{4-[(4-chlorobenzene)sulfmyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0080.041 3-{4-[(4-ethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.003 0.5333-{4-[(4-fluoro-2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0050.287 ylmethyl)urea3-{4-[(4-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0040.171 3-{4-[(4-methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3-0.002 0.091 ylmethyl)urea3-{4-[(4-methoxy-2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0080.352 ylmethyl)urea3-{4-[(5-chloro-2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0050.021 ylmethyl)urea3-{4-[(5-fluoro-2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0020.004 ylmethyl)urea3-{4-[(5-fluoro-2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0040.489 ylmethyl)urea3-{4-[2-chloro-6-(propan-2-yl)pyridine-3-sulfonyl]phenyl}-1-(pyridin-3-0.003 0.006 ylmethyl)urea N,N-dimethyl-4-[(4-{[(pyridin-3- 0.005 0.053ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide1-(4-{[2-(morpholin-4-ylmethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-0.0036 0.0079 ylmethyl)urea1-(4-{[3-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3- 0.00220.0980 ylmethyl)urea1-(4-{[3-(cyclopropylmethoxy)benzene]sulfonyl}phenyl)-3-(pyridin-3-0.0086 0.1-1 ylmethyl)urea1-(4-{[4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3- 0.00550.0550 ylmethyl)urea1-(4-{[4-(morpholin-4-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3- 0.00180.0147 ylmethyl)urea1-(pyridin-3-ylmethyl)-3-[4-(3,3,5-trimethylazepane-1- 0.0020 0.0092sulfonyl)phenyl]urea1-(pyridin-3-ylmethyl)-3-{4-[(3-sulfamoylbenzene)sulfonyl]phenyl}urea0.0038 0.1-1 1-(pyridin-3-ylmethyl)-3-{4-[6-(trifluoromethyl)pyridine-3-0.0279   1-10 sulfonyl]phenyl}urea1-[4-({3-[(morpholin-4-yl)carbonyl]benzene}sulfonyl)phenyl]-3-(pyridin-0.0050 0.1-1 3-ylmethyl)urea1-[4-(1H-indole-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.00160.0134 1-[4-(1H-indole-7-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.0005 0.00341-[4-(2,3-dihydro-1,4-benzodioxine-6-sulfonyl)phenyl]-3-(pyridin-3-0.0011 0.1-1 ylmethyl)urea1-[4-(2,3-dihydro-1-benzofuran-7-sulfonyl)phenyl]-3-(pyridin-3- 0.00110.0105 ylmethyl)urea1-[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.0043 0.1-11-[4-(isoquinoline-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.00140.0083 1-[4-(phenoxathiine-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea0.0029 0.00181-{4-[(3-benzoylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea0.0044   1-101-{4-[(3-cyanobenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.00800.1-1 1-{4-[(3-phenylbenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea0.0068 0.1-11-{4-[(4-cyanobenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.00760.1-1 1-{4-[(4-phenylbenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea0.0058 0.1-11-{4-[(pyridin-2-ylmethyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea0.0084   1-101-{4-[2-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3- 0.01600.1-1 ylmethyl)urea1-{4-[4-(2-phenylacetyl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-0.0030 0.9323 ylmethyl)urea1-{4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3- 0.00360.0304 ylmethyl)urea 2-fluoro-N-(propan-2-yl)-5-[(4-{[(pyridin-3- 0.02090.1-1 ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide2-methyl-N-{3-[(4-{[(pyridin-3- 0.0012 0.0101ylmethyl)carbamoyl]amino}benzene)sulfonyl]phenylJpropanamide3-(4-{[2-chloro-5-(trifluoromethoxy)benzene]sulfonyl}phenyl)-1-(pyridin-0.0063 0.1-1 3-ylmethyl)urea3-(4-{[2-methoxy-5-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-0.0014 0.0033 3-ylmethyl)urea3-(4-{[2-methyl-4-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.0118 0.1-1 ylmethyl)urea3-(4-{[3-(2-methylpropoxy)benzene]sulfonyl]phenyl)-1-(pyridin-3- 0.00330.1-1 ylmethyl)urea3-(4-{[3-(3,5-dimethyl-1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-0.0016 0.0159 (pyridin-3-ylmethyl)urea3-(4-{[3-(5-methyl-1,3,4-oxadiazol-2-yl)benzene]sulfonyl]phenyl)-1-0.0073 0.1-1 (pyridin-3-ylmethyl)urea3-(4-{[3-(dimethylsulfamoyl)benzene]sulfonyl]phenyl)-1-(pyridin-3-0.0033 0.0793 ylmethyl)urea3-(4-{[3-(ethanesulfonyl)benzene]sulfonyl]phenyl)-1-(pyridin-3- 0.00760.1-1 ylmethyl)urea3-(4-{[3-(ethylsulfamoyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.00720.1-1 ylmethyl)urea3-(4-{[3-(methoxymethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.00330.0933 ylmethyl)urea3-(4-{[3-(propane-1-sulfonamido)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.0016 0.0860 ylmethyl)urea3-(4-{[3-chloro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.0040 0.1-1 ylmethyl)urea3-(4-{[3-chloro-5-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.0013 0.0255 ylmethyl)urea3-(4-{[3-fluoro-4-(2,2,2-trifluoroethoxy)benzene]sulfonyl}phenyl)-1-0.0022 0.1-1 (pyridin-3-ylmethyl)urea3-(4-{[3-fluoro-4-(trifluoromethoxy)benzene]sulfonyl}phenyl)-1-(pyridin-0.0055 0.1-1 3-ylmethyl)urea3-(4-{[3-fluoro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-0.0041 0.1-1 ylmethyl)urea3-(4-{[3-fluoro-5-(2,2,2-trifluoroethoxy)benzene]sulfonyl]phenyl)-1-0.0011 0.0297 (pyridin-3-ylmethyl)urea3-(4-{[3-fluoro-5-(2-methylpropoxy)benzene]sulfonyl}phenyl)-1-(pyridin-0.0040 0.0564 3-ylmethyl)urea3-(4-{[3-fluoro-5-(trifluoromethyl)benzene]sulfonyl[phenyl)-1-(pyridin-3-0.0007 0.0576 ylmethyl)urea3-(4-{[4-(ethoxymethyl)benzene]sulfonyl[phenyl)-1-(pyridin-3- 0.00100.1-1 ylmethyl)urea3-(4-{[4-(propan-2-yl)benzene]sulfonyl[phenyl)-1-(pyridin-3- 0.00300.1-1 ylmethyl)urea3-(4-{[4-(propan-2-yloxy)benzene]sulfonyl[phenyl)-1-(pyridin-3- 0.00170.0291 ylmethyl)urea3-(4-{[4-fluoro-3-(2,2,2-trifluoroethoxy)benzene]sulfonyl[phenyl)-1-0.0021 0.0234 (pyridin-3-ylmethyl)urea3-(4-{[4-fluoro-3-(trifluoromethyl)benzene]sulfonyl[phenyl)-1-(pyridin-3-0.0015 0.0862 ylmethyl)urea3-(4-{4-[2-(3,4-dichlorophenyl)acetyl]piperazine-1-sulfonyl[phenyl)-1-0.0037   1-10 (pyridin-3-ylmethyl)urea3-(pyridin-3-ylmethyl)-1-[4-({4-[(pyrrolidin-1- 0.0013 0.0076yl)carbonyl]benzene}sulfonyl)phenyl]urea3-(pyridin-3-ylmethyl)-1-[4-(quinoline-3-sulfonyl)phenyl]urea 0.00280.0280 3-(pyridin-3-ylmethyl)-1-[4-(quinoline-6-sulfonyl)phenyl]urea0.0027 0.04413-(pyridin-3-ylmethyl)-1-[4-(quinoline-8-sulfonyl)phenyl]urea 0.00140.0022 3-[(4-{[(pyridin-3- 0.0080   1-10ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide3-[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0010 0.05993-[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0018 0.09253-[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0025 0.03543-[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0144 0.1-13-[4-(1-methyl-1H-indole-2-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0030 0.06353-[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0063 0.01313-[4-(2,4-dimethoxypyrimidine-5-sulfonyl)phenyl]-1-(pyridin-3- 0.00670.0210 ylmethyl)urea3-[4-(2-methoxypyrimidine-5-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0087 0.1-13-[4-(2-methylpyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0072 0.1-13-[4-(4-{[4-(propan-2-yl)phenyl]methyl[piperazine-1-sulfonyl)phenyl]-1-0.0358   1-10 (pyridin-3-ylmethyl)urea3-[4-(5-chloropyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0026 0.09823-[4-(5-fluoropyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0087 0.1-1 3-[4-(6-methoxynaphthalene-2-sulfonyl)phenyl]-1-(pyridin-3-0.0016 0.1-1 ylmethyl)urea3-[4-(6-methoxypyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0050 0.1-13-[4-(6-methylpyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea0.0049 0.1-13-{4-[(3,4-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0029 0.1-13-{4-[(3,5-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0019 0.1-13-{4-[(3-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0021 0.1-13-{4-[(3-chloro-4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00130.0929 ylmethyl)urea3-{4-[(3-chloro-4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00090.1-1 ylmethyl)urea3-{4-[(3-chloro-4-propoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00460.1-1 ylmethyl)urea3-{4-[(3-chloro-5-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00130.0272 ylmethyl)urea3-{4-[(3-chloro-5-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00180.0671 ylmethyl)urea3-{4-[(3-ethanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00110.0695 ylmethyl)urea3-{4-[(3-ethoxy-4-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00390.0283 ylmethyl)urea3-{4-[(3-ethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0017 0.08373-{4-[(3-ethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.00200.0708 3-{4-[(3-fluoro-4-propoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-0.0013 0.0585 ylmethyl)urea3-{4-[(3-fluoro-5-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00170.1-1 ylmethyl)urea3-{4-[(3-fluoro-5-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00170.0993 ylmethyl)urea3-{4-[(3-methanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00130.0761 ylmethyl)urea3-{4-[(3-methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00660.1-1 ylmethyl)urea3-{4-[(3-methoxy-4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00270.0179 ylmethyl)urea3-{4-[(3-propoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0038 0.1-13-{4-[(4-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0020 0.1-13-{4-[(4-acetylphenyl)sulfanoyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0144   1-103-{4-[(4-chloro-3-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00440.0632 ylmethyl)urea3-{4-[(4-chlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0031 0.1-13-{4-[(4-ethoxy-3-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00120.0217 ylmethyl)urea3-{4-[(4-ethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0022 0.1-13-{4-[(4-fluoro-2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00200.0282 ylmethyl)urea3-{4-[(4-fluoro-3-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00370.0446 ylmethyl)urea3-{4-[(4-fluoro-3-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00370.1-1 ylmethyl)urea3-{4-[(4-methoxy-3,5-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-0.0021 0.0089 ylmethyl)urea3-{4-[(4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.0024 0.1-13-{4-[(5-acetyl-2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.00130.0017 ylmethyl)urea3-{4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}-1-(pyridin-3-0.0059 0.1-1 ylmethyl)urea3-{4-[3-chloro-2-(morpholin-4-yl)pyridine-4-sulfonyl]phenyl}-1-(pyridin-0.0040 0.0142 3-ylmethyl)urea3-{4-[4-(3-chlorophenyl)-4-hydroxypiperidine-1-sulfonyl]phenyl}-1-0.0052 0.9563 (pyridin-3-ylmethyl)urea3-{4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}-1-(pyridin-3- 0.00300.0749 ylmethyl)urea 3-chloro-N,N-diethyl-5-[(4-{[(pyridin-3- 0.00350.0017 ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide3-fluoro-N,N-dimethyl-5-[(4-{[(pyridin-3- 0.0015 0.0133ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide4-fluoro-N-(propan-2-yl)-3-[(4-{[(pyridin-3- 0.0154 0.1-1ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamideN-(2-hydroxyethyl)-3-[(4-{[(pyridin-3- 0.0078 0.1-1ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN-(2-methylpropyl)-3-[(4-{[(pyridin-3- 0.0097 0.1-1ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN-(propan-2-yl)-3-[(4-{[(pyridin-3- 0.0100 0.1-1ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN,N-diethyl-3-fluoro-5-[(4-{[(pyridin-3- 0.0012 0.0015ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN,N-diethyl-4-fluoro-3-[(4-{[(pyridin-3- 0.0024 0.0885ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN,N-dimethyl-3-[(4-{[(pyridin-3- 0.0074 0.1-1ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN-{3-[(4-{[(pyridin-3- 0.0015 0.0395ylmethyl)carbamoyl]amino}benzene)sulfonyl]phenyl}acetamideN-cyclopentyl-3-[(4-{[(pyridin-3- 0.0096 0.1-1ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN-cyclopropyl-3-[(4-{[(pyridin-3- 0.0064 0.1-1ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN-ethyl-3-[(4-{[(pyridin-3- 0.0067 0.1-1ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN-ethyl-4-[(4-{[(pyridin-3- 0.0013 0.0402ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamideN-methyl-5-[(4-{[(pyridin-3- 0.0038 0.0838ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyridine-2-carboxamiderel-3-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-1-(pyridin-0.0039 0.0135 3-ylmethyl)urea4-[(3-chlorophenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6- 0.138 0.00712ylmethyl}benzamide4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-[2-(pyridin-3- 4.72 0.0312yl)ethyl]benzamide4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6-0.00216 0.0023 ylmethyl}benzamide N-[2-(pyridin-3-yl)ethyl]-4-{[3- 20.51.55 (trifluoromethoxy)phenyl]sulfamoyl[benzamideN-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-4-(1,2,3,4-tetrahydroisoquinoline-2-11.1 2.62 sulfonyl)benzamide N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-0.467 0.00858 (trifluoromethoxy)phenyl]sulfamoyl}benzamideN-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{8-oxa-3- 0.109 0.0271azabicyclo[3.2.1]octane-3-sulfonyl}benzamide4-(benzenesulfonyl)-N-(pyridin-3-yl)benzamide 1.89 2.734-(benzenesulfonyl)-N-(pyridin-4-yl)benzamide 0.651 1.314-(benzenesulfonyl)-N-(pyridin-3-ylmethyl)benzamide 0.0805 0.216N-[2-(pyridin-3-yl)ethyl]-4-{[3- 9.37 0.374(trifluoromethoxy)benzene]sulfonyl}benzamideN-(1,3-benzothiazol-6-ylmethyl)-4-[(3-chlorobenzene)sulfonyl]benzamide11.4 0.00971N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethoxy)benzene]sulfonyl}benzamide0.139 0.0018N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethyl)benzene]sulfonyl}benzamide0.00703 0.004334-(benzenesulfonyl)-N-{imidazo[1,2-a]pyridin-7-ylmethyl}benzamide 0.03080.0259 N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-[(3- 0.0192 0.00354methoxybenzene)sulfonyl]benzamide4-[(3-chlorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6- 0.0121 0.00639ylmethyl}benzamide4-[(2-chlorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide0.0195 0.003924-[(3,5-difluorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide0.0177 0.005713-[(5-fluoropyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea0.024 0.7523-[(6-aminopyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea0.0085 0.07141-[(3-aminophenyl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea 0.011 2.543-[4-(benzenesulfonyl)phenyl]-1(pyridin-3-ylmethyl)urea 0.0035 0.163-[4-(benzenesulfonyl)phenyl]-1-{[6-(dimethylamino)pyridin-3- >30 27.6yl]methyl]urea3-{4-[(4-bromobenzene)sulfonyl]phenyl]-1-(pyridin-3-ylmethyl)urea 0.0030.239 3-{4-[(4-chlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.00452 0.2413-{4-[(4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea0.00433 0.1411-[4-(piperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.0486 >2

Xenograft Studies:

C.B-17-1gh-1b-Prkdc^(scid) mice (female) were injected s.c. with 5×10⁶A2780 cells (NCI) in the left flank. 10-12 days later when tumorsreached 100-200 mm3 in size, mice were randomized into treatment groupsof 8 mice per group including vehicle control and reference standardgroups. The compounds were formulated in 60:30:10 PEG-400:D5W: Ethanoland administered p.o., at the dose volume of 10 ml/kg BID for a durationof 5 or 10 days. The dose used for efficacy was selected from the MTD(Maximum Tolerated Dose) study. Mice were weighed and tumors measuredusing vernier calipers every alternate day. Tumor volume was calculatedaccording to the formula (length×width²)/2. All animal work was approvedby the Institutional Animal Care and Use Committee of BiologicalResource Centre, Singapore.

Results:

The following compound produced tumor regression.1-(4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; and1-(pyridin-3-ylmethyl)-3-(4-{[2-(trifluoromethoxy)benzene]sulfonyl}phenyl)urea.The following compound produced tumor stasis:3-{4-[(4-chloro-2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea;1-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea;3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; and1-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea.The following compounds delayed tumor growth:1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea;3-(4-{[2-methoxy-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea;1-(4-{[(1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea;3-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea;3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}urea;1-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea;3-{4-[(2-chloro-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea;1-{4-[(naphthalen-1-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea;3-{4-[(3-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea;3-{4-[(5-chloro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea.3-{4-[(4-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea;1-[4-(benzenesulfonyl)phenyl]-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea;and1-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea

While the present invention has been described in conjunction with thespecific embodiments set forth above, many alternatives, modificationsand other variations thereof will be apparent to those of ordinary skillin the art. All such alternatives, modifications and variations areintended to fall within the spirit and scope of the present invention.

1. A compound of Formula IIIA:

or a pharmaceutically acceptable salt thereof, wherein: R^(a) is present 4 times, each R^(a) is independently selected from the group consisting of hydrogen, amino, oxo, halo, alkoxy, alkyl, haloalkyl, —N(alkyl)₂, —NH(CO)O— alkyl, 1H-pyrazole, 1H-imidazole, and —C(O)NH₂; the pyridine to which R^(a) is attached can comprise a N-oxide formed with its N atom member; R¹ is —NR³R⁴; R³ is H, alkyl or —S(O)₂alkyl; R⁴ is alkyl, hydroxyalkyl, —S(O)₂alkyl, —(CH₂)_(q)cycloalkyl, —(CH₂)_(q)heterocycloalkyl, aryl, or arylalkyl-; wherein each of said cycloalkyl, aryl, or heterocycloalkyl of R⁴ is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents which can be the same or different and are independently selected from the group consisting of: halo, cyano, alkyl, hydroxyl, hydroxyalkyl, hydroxyalkoxy, haloalkyl, alkoxy, alkylalkoxy, haloalkoxy, arylalkenyl-, aryloxy, benzyloxy, oxo, —(CH₂)_(q)—NR^(b)R^(c), —(CH₂)_(q)—CONR^(b)R^(c), —S(O)₂-alkyl, —S(O)₂NH-alkyl, —S(O)₂-heterocycloalkyl, —S(O)₂—CF₃, —C(O)alkyl, —C(O)aryl, —C(O)alkylenylaryl, —C(O)O-alkyl, —(CH₂)_(q)cycloalkyl, cycloalkylalkoxy-, aryl, arylalkyl-, —(CH₂)_(q)heteroaryl, and —(CH₂)_(q)heterocycloalkyl; wherein each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl may be substituted by one or more halo, nitro, haloalkyl, haloalkoxy, oxo, cyano, alkyl, haloalkyl, or alkoxy; R^(b) and R^(c) are independently selected from the group consisting of H, alkyl, hydroxyalkyl, alkoxy, aryl, alkoxyalkyl, —S(O)₂alkyl and cycloalkyl; or R^(b) and R^(c) can form a 5 or 6 membered heterocycloalkyl group together with the nitrogen atom to which they are attached, wherein said heterocycloalkyl group may contain one or more additional heteroatom(s) selected from the group consisting of N, S and O; and q is 0 or 1; with the proviso that the compound of Formula IIIA is not: N,N-diethyl-4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide. 2-33. (canceled)
 34. The compound of claim 1, wherein R³ is H or —S(O)₂alkyl.
 35. The compound of claim 1, wherein R⁴ is alkyl, hydroxyalkyl, —S(O)₂alkyl, —(CH₂)_(q)cycloalkyl, or —(CH₂)_(q)heterocycloalkyl.
 36. The compound of claim 34, wherein R⁴ is hydroxyalkyl, —S(O)₂alkyl, —(CH₂)_(q)cycloalkyl, —(CH₂)_(q)heterocycloalkyl, aryl, or arylalkyl-.
 37. The compound of claim 1, wherein R⁴ is hydroxyalkyl, —S(O)₂alkyl, —(CH₂)_(q)cycloalkyl, —(CH₂)_(q)heterocycloalkyl, aryl, or arylalkyl-.
 38. The compound of claim 1, wherein R³ is H and R⁴ is substituted aryl.
 39. The compound of claim 38, wherein R³ is H and R⁴ is aryl substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of cyano, hydroxyl, hydroxyalkyl, hydroxyalkoxy, alkoxy, alkylalkoxy, haloalkoxy, arylalkenyl-, aryloxy, benzyloxy, oxo, —(CH₂)_(q)—NR^(b)R^(c), —(CH₂)_(q)—CONR^(b)R^(c), —S(O)₂-alkyl, —S(O)₂NH-alkyl, —S(O)₂-heterocycloalkyl, —S(O)₂—CF₃, —C(O)alkyl, —C(O)aryl, —C(O)alkylenylaryl, —C(O)O-alkyl, —(CH₂)_(q)cycloalkyl, cycloalkylalkoxy-, arylalkyl-, —(CH₂)_(q)heteroaryl, and —(CH₂)_(q)heterocycloalkyl.
 40. The compound of claim 1, wherein R³ is H and R⁴ is substituted arylalkyl-.
 41. The compound of claim 40, wherein R³ is H and R⁴ is arylalkyl-substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halo, cyano, alkyl, hydroxyl, hydroxyalkyl, hydroxyalkoxy, haloalkyl, alkoxy, alkylalkoxy, haloalkoxy, arylalkenyl-, aryloxy, benzyloxy, oxo, —(CH₂)_(q)—NR^(b)R^(c), —(CH₂)_(q)—CONR^(b)R^(c), —S(O)₂-alkyl, —S(O)₂NH-alkyl, —S(O)₂-heterocycloalkyl, —S(O)₂—CF₃, —C(O)alkyl, —C(O)aryl, —C(O)alkylenylaryl, —C(O)O-alkyl, —(CH₂)_(q)cycloalkyl, cycloalkylalkoxy-, arylalkyl-, —(CH₂)_(q)heteroaryl, and —(CH₂)_(q)heterocycloalkyl.
 42. A pharmaceutical composition, comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
 43. A compound selected from: 3-(4-{[2-methyl-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N-[2-(pyridin-3-yl)ethyl]-4-{[3-(trifluoromethoxy)benzene]sulfonyl}benzamide; 1-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea; 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-pyrazol-1-yl)pyridin-3-yl]methyl}urea; 3-(4-{[2-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 4-(benzenesulfonyl)-N-{imidazo[1,2-a]pyridin-7-ylmethyl}benzamide; 4-(benzenesulfonyl)-N-(pyridin-3-ylmethyl)benzamide; 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-imidazol-1-yl)pyridin-3-yl]methyl}urea; 3-{[({4-[(4-chlorobenzene)sulfinyl]phenyl}carbamoyl)amino]methyl}pyridin-1-ium-1-olate; N,N-dimethyl-4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[2-methoxy-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-[4-(benzenesulfonyl)phenyl]-3-(1H-pyrazol-3-ylmethyl)urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethoxy)benzene]sulfonyl}benzamide; 1-{[4-(benzenesulfonyl)phenyl]methyl}-3-(quinolin-6-yl)urea; 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(dimethylamino)pyridin-3-yl]methyl}urea; 1-[6-(benzenesulfonyl)pyridin-3-yl]-3-(pyridin-3-ylmethyl)urea; 1-[(3-aminophenyl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea; 3-{4-[(4-chlorobenzene)sulfinyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 4-[(2-chlorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide; 4-[(3-chlorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide; 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(2-methoxyethoxy)pyridin-3-yl]methyl}urea; 1-{4-[(2-phenoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-[4-(benzenesulfonyl)phenyl]-3-{5H,6H,7H,8H-imidazo[1,2-a]pyridin-6-ylmethyl}urea; 3-{4-[(2-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(benzenesulfonyl)phenyl]-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea; 3-(4-{[3-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(benzenesulfonyl)phenyl]-1-(quinolin-6-yl)urea; 1-{4-[(4-fluorobenzene)sulfonyl]phenyl)}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethyl)benzene]sulfonyl}benzamide; 4-[(3,5-difluorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide; 3-{4-[(4-methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-[(3-methoxybenzene)sulfonyl]benzamide; 1-(4-{8-oxatricyclo[7.4.0.0², ⁷]trideca-1 (9),2(7),3,5,10,12-hexaene-6-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; N-(1,3-benzothiazol-6-ylmethyl)-4-[(3-chlorobenzene)sulfonyl]benzamide; 1-[4-(benzenesulfonyl)phenyl]-3-{thieno[2,3-c]pyridin-2-ylmethyl}urea; 1-(4-benzoylphenyl)-3-(pyridin-3-ylmethyl)urea; 3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3-yl)urea; 4-(benzenesulfonyl)-N-(pyridin-3-yl)benzamide; 4-(benzenesulfonyl)-N-(pyridin-4-yl)benzamide; 3-{4-[4-(3-methoxyphenyl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(phenylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-4-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{8-methyl-2,8-diazaspiro[5.5]undecane-2-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[4-(trifluoromethyl)phenyl]piperazine-1-sulfonyl}phenyl)urea; 3-{4-[(3,4-difluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-methyl-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyridine-2-carboxamide; 3-{4-[(4-chloro-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(3-methoxyphenyl)pentan-3-yl]sulfamoyl)}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-methoxy-3-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-chloro-3-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(morpholin-4-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; (2S)-N,N-dimethyl-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidine-2-carboxamide; methyl 4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazine-1-carboxylate; 3-{4-[(2-methoxyethyl)(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[4-(2H-1,3-benzodioxol-5-yl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-(propan-2-yl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[(2-methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-fluoro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(cycloheptylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-{4-[4-(pyrazin-2-yl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(5-methylpyridin-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2-methoxyphenyl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[(1R,2R,3R,5 S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl]sulfamoyl}phenyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[6-(trifluoromethyl)pyridin-2-yl]piperazine-1-sulfonyl}phenyl)urea; 3-{4-[4-(2-methylphenyl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(6-ethylpyridin-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-cyclopropyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}urea; 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrimidin-5-ylmethyl)urea; 3-(4-{[2-(3-methoxyphenyl)ethyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N-[(3R)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidin-3-yl]acetamide; 1-{4-[(4-phenylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2,4-difluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(dimethylsulfamoyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methoxy-6-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methanesulfonylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-chloro-2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-methyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide; 3-{4-[(4-chloro-2-methoxy-5-methylphenyl)sulfamoyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(1,5-dimethyl-1H-pyrazol-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(2-methoxyethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,4-dimethylphenyl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-(4-{methyl[(1 S)-1-phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{8-azaspiro[4.5]decane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[(5-chloro-2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,4-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,5-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}benzamide; 1-{4-[(5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-(4-{4-[2-(morpholin-4-yl)-2-oxoethyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-{4-[(3-benzoylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(6-methoxypyridin-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-4-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-ethyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[4-(2-methoxyethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(6-methoxynaphthalene-2-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[4-(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea; 3-{4-[cyclohexyl(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-(4-chlorophenoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-ethylphenyl)sulfamoyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-[4-({4-[(pyrrolidin-1-yl)carbonyl]benzene}sulfonyl)phenyl]urea; 3-(4-{[3-(2-hydroxyethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-2,6-dimethylphenyl)sulfamoyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,5-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-bromophenyl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methylpyridin-4-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-fluoro-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[(3,4-difluorophenyl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea; 4-(piperidine-1-sulfonyl)phenyl N-(pyridin-3-ylmethyl)carbamate; 3-{4-[(4-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[2-(3,4-dichlorophenyl)acetyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-({2-[(2S)-2-hydroxypropoxy]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-[4-(1H-indole-7-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-{4-[(1-phenylcyclopentyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-{4-[(3-phenylbenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-{4-[(pyridin-2-yl)sulfamoyl]phenyl}) -3-(pyridin-3-ylmethyl)urea; (3 S)-N,N-diethyl-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino)}benzene)sulfonyl]piperidine-3-carboxamide; 1-(4-{[(1 S,2S,4R)-bicyclo[2.2.1]heptan-2-yl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3-chlorophenyl)-4-cyanopiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-(4-methanesulfonylpiperazine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-ethoxy-2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-propylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-cyano-4-(4-methoxyphenyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-[3-(piperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3-fluorophenoxy)piperidine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(pyridin-3-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-(4-{[2-chloro-5-(trifluoromethoxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 2-methyl-N-{3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]phenyl}propanamide; 1-[4-(cyclohexylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-[4-(piperidine-1-sulfonyl)phenyl]-1-[1-(pyridin-3-yl)ethyl]urea; 1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-4-carboxamide; 3-{4-[(2-tert-butylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-chloro-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-fluoro-3-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{3-[(2-oxopyrrolidin-1-yl)methyl]piperidine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-(4-{[2-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-{4-[(2,4,6-trimethylphenyl)sulfamoyl]phenyl}urea; 3-[4-(piperidine-1-sulfonyl)phenyl]-1-[2-(pyridin-3-yl)ethyl]urea; 1-[4-(4-cyclohexylpiperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-chloro-4-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-fluoro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-(methyl sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,5-dichlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea; N-(propan-2-yl)-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide; N,N-diethyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide; 1-(4-{[4-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3,5-dichloropyridin-4-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(cyclobutylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[4-(trifluoromethyl)pyridin-2-yl]piperazine-1-sulfonyl}phenyl)urea; 1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl)}-3-(pyridin-3-ylmethyl)urea; 1-[4-(4-benzyl-1,4-diazepane-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; N-[(3 S)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidin-3-yl]acetamide; N,N-dimethyl-2-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 1-{4-[(2H-1,3-benzodioxol-5-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-chloro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,4-difluorophenyl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-[4-(diethyl sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; N-(2-methylpropyl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[3-(difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-methoxy-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2-ethoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-ethyl-4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[3-(propan-2-yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-{4-[(3-phenylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-(4-{[(3-fluorophenyl)methyl](methyl)sulfamoyl phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-ethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(benzylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methoxypyridin-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3 S)-3-methyl-4-(4-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[4-(piperidin-1-yl)piperidine-1-sulfonyl]phenyl)}-3-(pyridin-3-ylmethyl)urea; 3-[4-(butylsulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-methylpyridin-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,4-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(3-cyanophenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-(dimethylsulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[methanesulfonyl(piperidin-4-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[(4-fluorophenyl)carbonyl]piperidine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3 S)-4-(4-methoxyphenyl)-3-methylpiperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[methyl(oxolan-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-(difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-methyl-4-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{4-[3-(morpholin-4-yl)propyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(propane-1-sulfonamido)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(5-chloro-2-methylphenyl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(naphthalen-1-yl)sulfamoyl]phenyl)}-3-(pyridin-3-ylmethyl)urea; 3-(4-{[3-chloro-4-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-{4-[4-(2H-1,3-benzodioxol-5-ylmethyl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; N-methyl-N-phenyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide; 1-(4-{4-[(furan-2-yl)carbonyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(5-chloro-2-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,6-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-chloro-N,N-diethyl-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-[2-fluoro-4-(piperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 1-(pyridin-3-ylmethyl)-3-[4-({[3-(trifluoromethyl)phenyl]methyl}) sulfamoyl)phenyl]urea; pyridin-3-ylmethyl N-[4-(piperidine-1-sulfonyl)phenyl]carbamate; 1-(4-{[3-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(2-hydroxyethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-benzyl-1-[4-(piperidine-1-sulfonyl)phenyl]urea; 3-{4-[(2-hydroxyethyl)(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[4-(trifluoromethane)sulfonylphenyl]sulfamoyl)}phenyl)urea; 3-{4-[(3-ethanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-chloro-3-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methylpropyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-(2-hydroxyethyl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-{4-[(3-chloro-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-chlorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[methyl(2-methylpropyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{methyl[(1R)-1-phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2-chlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-({2-[(1 S)-1-hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,5-difluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-{[2-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-tert-butylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{methyl[2-(4-methylphenyl)ethyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,6-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]phenyl}acetamide; 1-(4-{4-[2-oxo-2-(piperidin-1-yl)ethyl]piperazine-1-sulfonyl)}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(3,5-dimethyl-1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(methoxymethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{[2-(morpholin-4-ylmethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; N-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-4-(1,2,3,4-tetrahydroisoquinoline-2-sulfonyl)benzamide; methyl 4-{[(pyridin-3-ylmethyl)carbamoyl]amino)}benzoate; 3-(4-{[2-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-{4-[(3,4,5-trifluorophenyl)sulfamoyl]phenyl}urea; N,N-diethyl-4-fluoro-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 1-(4-{[4-(piperidine-1-sulfonyl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2,4-dichlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(ethyl sulfamoyl)benzene]sulfonyl}phenyl)-1-(pyri din-3-ylmethyl)urea; 3-{4-[(2,2-dimethylpropyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(dibenzylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; (2S)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidine-2-carboxamide; 3-{4-[benzyl(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3-chloropyridin-2-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(propan-2-yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N,N-diethyl-3-fluoro-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[4-(methoxymethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-4-carboxamide; 3-{4-[(propan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-({3-[(morpholin-4-yl)carbonyl]benzene}sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-fluorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-ethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[benzyl(propan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-({[4-(dimethylamino)phenyl]methyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[benzyl(ethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-acetylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(4-{[(2R)-oxolan-2-yl]carbonyl}piperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 2-methyl-N-{1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino)}benzene)sulfonyl]piperidin-4-yl}propanamide; 1-(pyridin-3-ylmethyl)-3-(4-{[4-(trifluoromethoxy)phenyl]sulfamoyl)}phenyl)urea; 3-(pyridin-3-ylmethyl)-1-(4-{[4-(pyrrolidin-1-yl)phenyl]sulfamoyl)}phenyl)urea; 3-(4-{[(3-chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(ethanesulfonyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(4-hydroxypiperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(hydroxymethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-acetylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-ethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 4-fluoro-N-(propan-2-yl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-{4-[4-(3-chlorophenyl)-4-hydroxypiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3 S)-3-methyl-4-(3-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,3-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,3-dichlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(4-benzylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-(4-{[(4-phenylphenyl)methyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-{4-[(5,6,7,8-tetrahydronaphthalen-1-yl)sulfamoyl]phenyl}urea; 3-{4-[(4-fluoro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(4-ethynylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-chloro-4,6-dimethylphenyl)sulfamoyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2R)-2-benzylpiperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrazin-2-ylmethyl)urea; 1-{4-[(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(diethylamino)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-fluorophenyl)(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4-{3-oxa-8-azabicyclo[3.2.1]octane-8-sulfonyl}phenyl)urea; 3-{4-[(3-fluoro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-(4-methanesulfonylpiperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-{4-[(2 S)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-sulfonyl]phenyl}urea; 3-(4-{4-[(morpholin-4-yl)carbonyl]piperidine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[3-(2-chloro-4-fluorophenoxy)piperidine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[4-chloro-3-(trifluoromethyl)phenyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[bis(4-fluorophenyl)methyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{[3-(benzyloxy)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-(4-{[3-(pyrrolidin-1-yl)phenyl]sulfamoyl}phenyl)urea; 3-{4-[4-(3,4-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[3-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea; 3-{4-[(2-ethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-chloro-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[(2-fluorophenyl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea; 1-{4-[(4-phenoxyphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-{4-[4-(azepan-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 1-(4-{[4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-{4-[(cyclohexylmethyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(4-ethylphenyl)sulfamoyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-bromophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,4-dichlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-tert-butylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[4-(2-oxo-2,3-dihydro-1H-indol-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-[(6-isocyanopyridin-3-yl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea; 3-(4-{[2-(3-chlorophenyl)ethyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{[3-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-{4-[3-(pyrrolidin-1-yl)pyrrolidine-1-sulfonyl]phenyl}urea; 1-[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[3-(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea; 3-{4-[methyl(2-phenylethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[(4-fluorophenyl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea; 3-[4-(tert-butylsulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-[4-(4-phenylpiperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(5-methylpyrimidin-2-yl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[2-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea; 3-{4-[(2-acetylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-bromo-3-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-{2-oxa-8-azaspiro[4.5]decane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-{4-[4-(2-phenylacetyl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-{4-[4-(3-phenylprop-2-en-1-yl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-{4-[(3-sulfamoylbenzene)sulfonyl]phenyl}urea; N-methyl-2-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 3-(4-{[4-(propan-2-yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-hydroxyethyl)(propan-2-yl)sulfamoyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(adamantan-1-yl)sulfamoyl]phenyl)}-3-(pyridin-3-ylmethyl)urea; 1-{4-[(2R)-2-(morpholin-4-ylmethyl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3,5-dichlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-fluoro-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-{3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]phenyl}acetamide; N-methyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 3-{4-[4-(4-chlorophenyl)-4-cyanopiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-methyl-3-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-[4-(4-phenylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-fluoro-N,N-dimethyl-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; N-[2-(pyridin-3-yl)ethyl]-4-{[3-(trifluoromethoxy)phenyl]sulfamoyl)}benzamide; 3-{4-[cyclohexyl(ethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3,4-dichlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-fluoro-3-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-fluoro-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(4-{[4-(propan-2-yl)phenyl]methyl}piperazine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[3-(trifluoromethyl)phenyl]piperazine-1-sulfonyl}phenyl)urea; 1-[4-(cyclopropylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-[2-(pyridin-3-yl)ethyl]benzamide; 3-{4-[(3-aminophenyl)(methanesulfonyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2,3-dihydro-1H-inden-5-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-(4-{[3-chloro-4-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[1-(3-methoxyphenyl)-4-methylcyclohexyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-chloronaphthalen-1-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-acetyl-2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-chloro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine]-1′-ylsulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,4-dimethoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1-(pyridin-3-yl)urea; N-{1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidin-4-yl}acetamide; 3-{4-[(3-fluoro-4-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2-phenylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-(4-{4-[(2-oxopyrrolidin-1-yl)methyl]piperidine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-{4-[(1-phenylcyclohexyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-(4-{4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-{4-[(4-sulfamoylphenyl)sulfamoyl]phenyl}urea; 3-(4-{4-[(4-tert-butylphenyl)methyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-(4-{[2-(1H-pyrrol-1-yl)phenyl]sulfamoyl}phenyl)urea; 3-(4-{4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N,N-diethyl-2-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 1-{4-[(piperidin-1-yl)carbonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; N-ethyl-N-[(3 S)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino})benzene)sulfonyl]pyrrolidin-3-yl]acetamide; 3-(pyridin-3-ylmethyl)-1-{4-[4-(pyrimidin-2-yl)piperazine-1-sulfonyl]phenyl)}urea; 3-(pyridin-3-ylmethyl)-1-(4-{[(1 S,2S,3 S, 5R)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl]sulfamoyl}phenyl)urea; 3-{4-[(4-fluoro-3-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-phenylpropan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[(1R)-1-(4-chlorophenyl)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[(3-fluorophenyl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea; 3-{4-[4-cyano-4-(4-methylphenyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(3-phenoxyphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2,5-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(dipropylamino)piperidine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-fluorophenyl)methyl](methyl)sulfamoyl phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-{4-[(3 S)-3-[(pyrrolidin-1-yl)carbonyl]piperidine-1-sulfonyl]phenyl}urea; 3-{4-[(3-bromophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2-phenoxyphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-(4-{4-[1-(4-chlorophenyl)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 1-{4-[(4-phenylbenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3,5-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-methylphenyl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-[4-(4-acetyl-1,4-diazepane-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; N-cyclopentyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 1-(4-{[4-(morpholin-4-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-[4-({3-[(1 S)-1-hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,5-difluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,5-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[ethyl(phenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[2-(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea; 3-(4-{[3-(5-methyl-1,3,4-oxadiazol-2-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-({4-[(1 S)-1-hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 4-[(3-chlorophenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide; 3-{4-[(4-tert-butyl-2-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(cyclopentylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-(4-{4-[2-(diethylamino)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-chlorophenyl)piperazine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(3-fluorophenyl)ethyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[methyl({[3-(trifluoromethyl)phenyl]methyl})sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-{[3-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[(2-chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-acetylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3,4-dimethoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; (2R)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino)}benzene)sulfonyl]pyrrolidine-2-carboxamide; 3-(4-{[(3-methoxyphenyl)methyl] sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(ethylsulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-sulfonyl}phenyl)urea; 3-{4-[(4-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-fluoro-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(4-cyanophenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-5-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-(4-((2-methoxyethyl)(methyl)amino)piperidin-1-yl sulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2,4-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-(4-{[2-(pyrrolidin-1-yl)phenyl]sulfamoyl}phenyl)urea; 3-{4-[(3-methoxy-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-nitrophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2-chloro-4-fluorophenoxy)piperidine-1-sulfonyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-chloro-2-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-chloro-3-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,3-dichlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)urea; 2-fluoro-N-(propan-2-yl)-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[2-(2-hydroxyethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3-chlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2 S)-2-ethylpiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-{[4-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-{4-[(4-cyanobenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-bromophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,4-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-iodophenyl)sulfamoyl]phenyl)}-1-(pyridin-3-ylmethyl)urea; 1-{4-[2-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethoxy)phenyl]sulfamoyl}benzamide; and 4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide, or a pharmaceutically acceptable salt thereof.
 44. A pharmaceutical composition, comprising a compound of claim 43, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 